Research Topics
Genomes and Genes
| A SancarSummaryAffiliation: University of North Carolina Country: USA Publications
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Publications
Nucleotide excision repairJoyce T Reardon
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
Prog Nucleic Acid Res Mol Biol 79:183-235. 2005
A role for cryptochromes in sleep regulationJonathan P Wisor
Dept of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
BMC Neurosci 3:20. 2002..We studied sleep in cry1,2-/- mice under baseline conditions as well as under conditions of constant darkness and enforced wakefulness to determine whether cryptochromes influence sleep regulatory processes...- Cryptochrome: the second photoactive pigment in the eye and its role in circadian photoreceptionA Sancar
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 7260, USA
Annu Rev Biochem 69:31-67. 2000..Research on cryptochromes may provide new understanding of human diseases such as seasonal affective disorder and delayed sleep phase syndrome... - Regulation of the mammalian circadian clock by cryptochromeAziz Sancar
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
J Biol Chem 279:34079-82. 2004 - Molecular mechanisms of mammalian DNA repair and the DNA damage checkpointsAziz Sancar
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 7260, USA
Annu Rev Biochem 73:39-85. 2004..In this review the molecular mechanisms of DNA repair and the DNA damage checkpoints in mammalian cells are analyzed... - Structure and function of DNA photolyase and cryptochrome blue-light photoreceptorsAziz Sancar
Department of Biochemistry and Biophysics, Mary Ellen Jones Building, CB 7260, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
Chem Rev 103:2203-37. 2003 - Circadian clock control of the cellular response to DNA damageAziz Sancar
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7260, USA
FEBS Lett 584:2618-25. 2010..These new insights are expected to guide development of novel mechanism-based chemotherapeutic regimens... - Purification and characterization of human DNA damage checkpoint Rad complexesL A Lindsey-Boltz
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Proc Natl Acad Sci U S A 98:11236-41. 2001..These findings constitute biochemical support for models regarding the roles of checkpoint Rads as damage sensors in the DNA damage checkpoint response of human cells... - Formation of a ternary complex by human XPA, ERCC1, and ERCC4(XPF) excision repair proteinsC H Park
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599
Proc Natl Acad Sci U S A 91:5017-21. 1994..We conclude that the XPA damage recognition protein makes a ternary complex with the ERCC1/ERCC4(XPF) heterodimer with a potential nuclease function... - Putative human blue-light photoreceptors hCRY1 and hCRY2 are flavoproteinsD S Hsu
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599, USA
Biochemistry 35:13871-7. 1996..We conclude that these newly discovered members of the photolyase/photoreceptor family are not photolyases and instead may function as blue-light photoreceptors in humans... - Molecular mechanism of transcription-repair couplingC P Selby
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599
Science 260:53-8. 1993..Thus, Mfd appears to target the transcribed strand for repair by recognizing a stalled RNAP and actively recruiting the repair enzyme to the transcription blocking lesion as it dissociates the stalled RNAP... - The other function of DNA photolyase: stimulation of excision repair of chemical damage to DNAZ Ozer
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599, USA
Biochemistry 34:15886-9. 1995..coli excision nuclease in vitro. In agreement with the in vitro data, in vivo experiments revealed that photolyase makes cells more resistant to cisplatin killing... - Role of mouse cryptochrome blue-light photoreceptor in circadian photoresponsesR J Thresher
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Science 282:1490-4. 1998..These data are consistent with the hypothesis that CRY2 protein modulates circadian responses in mice and suggest that cryptochromes have a role in circadian photoreception in mammals... - Transcription-repair coupling and mutation frequency declineC P Selby
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599
J Bacteriol 175:7509-14. 1993 - Human DNA repair excision nuclease. Analysis of the roles of the subunits involved in dual incisions by using anti-XPG and anti-ERCC1 antibodiesT Matsunaga
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599, USA
J Biol Chem 270:20862-9. 1995..Using a defined system for excision repair we also demonstrate that the 3' incision can occur without the 5' incision, leading us to conclude that under certain conditions the two incisions can occur independently... - Circadian regulation of cryptochrome genes in the mouseY Miyamoto
Department of Biochemistry and Biophysics, Mary Ellen Jones Bldg, CB 7260, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7260, USA
Brain Res Mol Brain Res 71:238-43. 1999..Third, mutation in Cry2 causes a phase delay in Cry1 and mPer1 expression both in the SCN and internal organs relative to wild-type animals. Finally, no obvious periodicity in mCry2 expression was seen in all tissues tested... - No "End of History" for photolyasesA Sancar
Department of Biochemistry and Biophysics, University of Nor Carolina School of Medicine, Chapel Hill, 27599, USA
Science 272:48-9. 1996 - Reaction mechanism of (6-4) photolyaseX Zhao
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 7260, USA
J Biol Chem 272:32580-90. 1997..Taken together, the data are consistent with photoinduced electron transfer from reduced FAD to substrate, in a manner analogous to the cyclobutane pyrimidine dimer photolyase... - Structure and function of transcription-repair coupling factor. II. Catalytic propertiesC P Selby
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599
J Biol Chem 270:4890-5. 1995..In vitro, strand-specific repair is not dependent on the MutL and MutS proteins which have recently been implicated in preferential repair in vivo... - Human transcription release factor 2 dissociates RNA polymerases I and II stalled at a cyclobutane thymine dimerR Hara
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
J Biol Chem 274:24779-86. 1999.... - Structure and function of animal cryptochromesN Ozturk
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
Cold Spring Harb Symp Quant Biol 72:119-31. 2007..In mammals, CRYs participate in cell cycle regulation and the cellular response to DNA damage by controlling the expression of some cell cycle genes and by directly interacting with checkpoint proteins... - Cockayne syndrome group B protein enhances elongation by RNA polymerase IIC P Selby
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7260, USA
Proc Natl Acad Sci U S A 94:11205-9. 1997..Thus a deficiency in transcription elongation may contribute to the CS phenotype... - Human blue-light photoreceptor hCRY2 specifically interacts with protein serine/threonine phosphatase 5 and modulates its activityS Zhao
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599 7260, USA
Photochem Photobiol 66:727-31. 1997..We found that hCRY2, but not the highly homologous (6-4) photolyase, inhibits the phosphatase activity of PP5. This inhibition may be on the pathway of blue-light signal transduction reaction in humans... - Escherichia coli mfd mutant deficient in "mutation frequency decline" lacks strand-specific repair: in vitro complementation with purified coupling factorC P Selby
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599
Proc Natl Acad Sci U S A 88:11574-8. 1991..We conclude that mfd is, most likely, the gene encoding the transcription-repair coupling factor... - The general transcription-repair factor TFIIH is recruited to the excision repair complex by the XPA protein independent of the TFIIE transcription factorC H Park
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599
J Biol Chem 270:4896-902. 1995..This latter interaction has no apparent role in general excision repair but may be relevant in the transcription-coupled repair reaction... - Coupling of human circadian and cell cycles by the timeless proteinKeziban Unsal-Kaçmaz
Department of Biochemistry and Biophysics, Mary Ellen Jones Building CB 7260, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Mol Cell Biol 25:3109-16. 2005.... - Purification and characterization of Drosophila melanogaster photolyaseS T Kim
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599, USA
Mutat Res 363:97-104. 1996..We overproduced the Drosophila melanogaster photolyase in Escherichia coli using the cloned gene. The enzyme contains FAD and folate and thus belongs in the folate class of enzymes but with an action spectrum peak at 420 nm... - Human transcription-repair coupling factor CSB/ERCC6 is a DNA-stimulated ATPase but is not a helicase and does not disrupt the ternary transcription complex of stalled RNA polymerase IIC P Selby
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
J Biol Chem 272:1885-90. 1997..CSB is a DNA-binding protein, and it also binds to XPA, TFIIH, and the p34 subunit of TFIIE. These interactions are likely to play a role in recruiting repair proteins to ternary complexes formed at damage sites... - Functional redundancy of cryptochromes and classical photoreceptors for nonvisual ocular photoreception in miceC P Selby
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Proc Natl Acad Sci U S A 97:14697-702. 2000.... - Post-incision steps of nucleotide excision repair in Escherichia coli. Disassembly of the UvrBC-DNA complex by helicase II and DNA polymerase ID K Orren
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599
J Biol Chem 267:780-8. 1992..The discovery of psoralen-UvrB photocross-linking offers the potential of active-site labeling... - Mechanisms of transcription-repair coupling and mutation frequency declineC P Selby
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599
Microbiol Rev 58:317-29. 1994..Thus, the mechanism of strand-specific repair is well understood, but some questions remain regarding the precise mechanism of mutation frequency decline... - Structure and function of transcription-repair coupling factor. I. Structural domains and binding propertiesC P Selby
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599
J Biol Chem 270:4882-9. 1995..Dissociation of the ternary complex upon hydrolysis of ATP also requires the carboxyl terminus of TRCF. Finally, residues 1-378 bind to UvrA and deliver the damage recognition component of the excision nuclease to the lesion... - Vitamin B2-based blue-light photoreceptors in the retinohypothalamic tract as the photoactive pigments for setting the circadian clock in mammalsY Miyamoto
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Proc Natl Acad Sci U S A 95:6097-102. 1998.... - DNA excision repairA Sancar
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599, USA
Annu Rev Biochem 65:43-81. 1996..Individuals defective in excision repair exhibit a high incidence of cancer while individuals with a defect in coupling transcription to repair suffer from neurological and skeletal abnormalities... - Isolation and characterization of two human transcription factor IIH (TFIIH)-related complexes: ERCC2/CAK and TFIIHJ T Reardon
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599, USA
Proc Natl Acad Sci U S A 93:6482-7. 1996..These data suggest that TFIIH* and ERCC2/CAK interact to form the TFIIH holoenzyme capable of efficiently assembling the pol II transcription initiation complex and directly participating in excision repair reactions... 
The human ATR-mediated DNA damage checkpoint in a reconstituted systemJun Hyuk Choi
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7260, United States
Methods 48:3-7. 2009..This system provides a powerful tool to gain insight into the molecular mechanism of the ATR pathway. Here we describe preparation of the checkpoint components and our specific kinase assay in more detail...- Reconstitution of RPA-covered single-stranded DNA-activated ATR-Chk1 signalingJun Hyuk Choi
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Proc Natl Acad Sci U S A 107:13660-5. 2010..We also find that TopBP1 is recruited to RPA-ssDNA in a manner dependent on ATRIP and that the N terminus of TopBP1 is required for efficient recruitment and activation of ATR kinase... - Active site of Escherichia coli DNA photolyase: mutations at Trp277 alter the selectivity of the enzyme without affecting the quantum yield of photorepairY F Li
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599
Biochemistry 29:5698-706. 1990.... - Human DNA damage checkpoint protein hRAD9 is a 3' to 5' exonucleaseT Bessho
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
J Biol Chem 275:7451-4. 2000..Our results suggest that exonucleolytic processing of primary DNA lesion by hRAD9 may contribute to DNA damage checkpoint response in humans... - Characterization of (6-4) photoproduct DNA photolyaseS T Kim
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599 7260
J Biol Chem 269:8535-40. 1994..Furthermore, we provide evidence that the (6-4) photoproduct photolyase converts the photoproduct to unmodified bases probably through an oxetane intermediate... - In vitro repair of oxidative DNA damage by human nucleotide excision repair system: possible explanation for neurodegeneration in xeroderma pigmentosum patientsJ T Reardon
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Proc Natl Acad Sci U S A 94:9463-8. 1997..Our results suggest that XP neurological disease may be caused by defective repair of lesions that are produced in nerve cells by reactive oxygen species generated as by-products of an active oxidative metabolism... - Reconstitution of human excision nuclease with recombinant XPF-ERCC1 complexT Bessho
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
J Biol Chem 272:3833-7. 1997.... - Characterization of transcription-repair coupling factors in E. coli and humansC P Selby
Department of Biochemistry and Biophysics, University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27599-7260, USA
Methods Enzymol 371:300-24. 2003 - Tipin-replication protein A interaction mediates Chk1 phosphorylation by ATR in response to genotoxic stressMichael G Kemp
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
J Biol Chem 285:16562-71. 2010..Our results therefore indicate that RPA-covered ssDNA not only supports recruitment and activation of ATR but also, through Tipin and Claspin, it plays an important role in the action of ATR on its critical downstream target Chk1... - Reconstitution of a human ATR-mediated checkpoint response to damaged DNAJun Hyuk Choi
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7260, USA
Proc Natl Acad Sci U S A 104:13301-6. 2007..This in vitro system provides a useful platform for mechanistic studies of the human DNA damage checkpoint response... - DNA repair excision nuclease attacks undamaged DNA. A potential source of spontaneous mutationsM E Branum
Department of Biochemistry and Biophysics, Mary Ellen Jones Bldg, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
J Biol Chem 276:25421-6. 2001..As resynthesis is invariably associated with mutations, we propose that gratuitous repair may be an important source of spontaneous mutations... - Isolation and characterization of functional domains of UvrAG M Myles
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599
Biochemistry 30:3834-40. 1991.... - Purification and characterization of the XPF-ERCC1 complex of human DNA repair excision nucleaseC H Park
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599, USA
J Biol Chem 270:22657-60. 1995..This complex also nicks supercoiled DNA weakly, and this nicking activity is stimulated by human replication protein A when the DNA contains UV damage... - Molecular anatomy of the human excision nuclease assembled at sites of DNA damageJoyce T Reardon
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
Mol Cell Biol 22:5938-45. 2002..Based on these results, we propose that RPA70 makes the initial contact with psoralen-damaged DNA but that within preincision complexes, it is RPA32 and XPD that are in close contact with the lesion... - Posttranslational regulation of the mammalian circadian clock by cryptochrome and protein phosphatase 5Carrie L Partch
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Proc Natl Acad Sci U S A 103:10467-72. 2006..Collectively, these findings indicate that PP5, CKIepsilon, and cryptochrome dynamically regulate the mammalian circadian clock... - Cooperative activation of the ATR checkpoint kinase by TopBP1 and damaged DNAJun Hyuk Choi
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7260, USA
Nucleic Acids Res 37:1501-9. 2009..Taken together, these findings suggest a cooperative activation mechanism for the ATR checkpoint kinase by TopBP1 and damaged DNA... - Recruitment of DNA damage checkpoint proteins to damage in transcribed and nontranscribed sequencesGuochun Jiang
Department of Biochemistry and Biophysics, Mary Ellen Jones Building CB 7260, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Mol Cell Biol 26:39-49. 2006.... - Order of assembly of human DNA repair excision nucleaseM Wakasugi
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 7260, USA
J Biol Chem 274:18759-68. 1999..We conclude that RPA and XPA are the initial damage sensing factors of human excision nuclease... - Preservation of light signaling to the suprachiasmatic nucleus in vitamin A-deficient miceC L Thompson
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Proc Natl Acad Sci U S A 98:11708-13. 2001..The data suggest that a non-opsin pigment is the primary circadian photoreceptor in the mouse... - Reconstitution of human claspin-mediated phosphorylation of Chk1 by the ATR (ataxia telangiectasia-mutated and rad3-related) checkpoint kinaseLaura A Lindsey-Boltz
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 7260, USA
J Biol Chem 284:33107-14. 2009..This in vitro system recapitulates essential components of the genetically defined ATR-signaling pathway... - Repair of DNA-polypeptide crosslinks by human excision nucleaseJoyce T Reardon
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Proc Natl Acad Sci U S A 103:4056-61. 2006..Our data suggest that, if coupled with proteolytic degradation of the crosslinked protein, the human excision nuclease may be the major enzyme system for eliminating protein-DNA crosslinks from the genome... - Purification and properties of human blue-light photoreceptor cryptochrome 2Sezgin Ozgur
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
Biochemistry 42:2926-32. 2003..These findings reveal new properties of this protein already known to function as a circadian photoreceptor and a light-independent negative transcriptional regulator of the clock genes... - Circadian control of XPA and excision repair of cisplatin-DNA damage by cryptochrome and HERC2 ubiquitin ligaseTae Hong Kang
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Proc Natl Acad Sci U S A 107:4890-5. 2010..These findings may be used as a guide for timing of cisplatin chemotherapy... - The human Tim/Tipin complex coordinates an Intra-S checkpoint response to UV that slows replication fork displacementKeziban Unsal-Kaçmaz
Lineberger Comprehensive Cancer Center, CB 7295, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Mol Cell Biol 27:3131-42. 2007.... - Cdc7-Dbf4 and the human S checkpoint response to UVCTimothy P Heffernan
Department of Pathology and Laboratory Medicine, University of North Carolina Chapel Hill, NC 27599, USA
J Biol Chem 282:9458-68. 2007..These findings implicate a Dbf4-dependent kinase as a possible target of the ATR- and Chk1-dependent S checkpoint response to UVC... - Cryptochrome, circadian cycle, cell cycle checkpoints, and cancerMichele A Gauger
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
Cancer Res 65:6828-34. 2005..We conclude that the effect of circadian clock disruption on cellular response to DNA damage and cancer predisposition in mice may depend on the mechanism by which the clock is disrupted... - Quaternary structure of ATR and effects of ATRIP and replication protein A on its DNA binding and kinase activitiesKeziban Unsal-Kaçmaz
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
Mol Cell Biol 24:1292-300. 2004..These findings suggest that the regulation and mechanism of action of ATR are fundamentally different from those of the other PIKK proteins... - RNA polymerase: the most specific damage recognition protein in cellular responses to DNA damage?Laura A Lindsey-Boltz
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7260, USA
Proc Natl Acad Sci U S A 104:13213-4. 2007 - Circadian regulation of DNA excision repair: implications for chrono-chemotherapyTae Hong Kang
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Cell Cycle 8:1665-7. 2009..Here we review the significance of the connection linking the circadian clock with nucleotide excision repair and discuss potential implications for chemotherapy... - Preferential binding of ATR protein to UV-damaged DNAKeziban Unsal-Kaçmaz
Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Proc Natl Acad Sci U S A 99:6673-8. 2002..In addition, damaged DNA stimulates the kinase activity of ATR to a significantly higher level than undamaged DNA. Our data suggest that ATR may function as an initial sensor in the DNA damage checkpoint response... - A mathematical model for human nucleotide excision repair: damage recognition by random order assembly and kinetic proofreadingKevin J Kesseler
Department of Pathology and Laboratory Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7255, USA
J Theor Biol 249:361-75. 2007..Finally, a comparison between the random order assembly with kinetic proofreading model and a sequential assembly model is made. This investigation reveals the advantages of the random order assembly/kinetic proofreading model... - Cloning, sequencing, expression and characterization of DNA photolyase from Salmonella typhimuriumY F Li
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599
Nucleic Acids Res 19:4885-90. 1991..The binding constant of S.typhimurium photolyase to thymine dimer in DNA is kD = 1.6 x 10(-9) M, and the quantum yield of photorepair at 384 nm is 0.5... - Purification and characterization of Escherichia coli and human nucleotide excision repair enzyme systemsJoyce T Reardon
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, USA
Methods Enzymol 408:189-213. 2006..This chapter outlines methods for expression and purification of these essential repair factors and provides protocols for performing each of the in vitro repair assays with either the E. coli or the human excision nuclease... - Repair of DNA-protein cross-links in mammalian cellsJoyce T Reardon
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
Cell Cycle 5:1366-70. 2006..Repair mechanisms are reasonably well-defined for groups 1 and 3, and suggested for groups 2 and 4. Our work is focused on the recognition and removal of DNA-protein cross-links in duplex DNA (group 4)... - A cryptochrome/photolyase class of enzymes with single-stranded DNA-specific photolyase activityChristopher P Selby
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7260, USA
Proc Natl Acad Sci U S A 103:17696-700. 2006..Here, we show that Cry-DASH proteins from bacterial, plant, and animal sources actually are photolyases with high degree of specificity for cyclobutane pyrimidine dimers in ssDNA... - Similar nucleotide excision repair capacity in melanocytes and melanoma cellsShobhan Gaddameedhi
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
Cancer Res 70:4922-30. 2010..We concluded that melanoma cells retain capacity for nucleotide excision repair, the loss of which probably does not commonly contribute to melanoma progression... - Photolyase/cryptochrome blue-light photoreceptors use photon energy to repair DNA and reset the circadian clockCarol L Thompson
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina, NC 27599 7260, USA
Oncogene 21:9043-56. 2002..Cryptochrome, which has a high degree of sequence identity to photolyase, works as the main circadian photoreceptor and as a component of the molecular clock in animals, including mammals, and regulates growth and development in plants... - Purification and characterization of DNA photolyasesGwendolyn B Sancar
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, USA
Methods Enzymol 408:121-56. 2006.... - The SWI/SNF chromatin-remodeling factor stimulates repair by human excision nuclease in the mononucleosome core particleRyujiro Hara
Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill, 27599, USA
Mol Cell Biol 22:6779-87. 2002.... - Effect of vitamin A depletion on nonvisual phototransduction pathways in cryptochromeless miceCarol L Thompson
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
J Biol Rhythms 19:504-17. 2004..These data demonstrate that both cryptochromes and opsins regulate nonvisual photoresponses... - Human claspin is a ring-shaped DNA-binding protein with high affinity to branched DNA structuresFunda Sar
Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
J Biol Chem 279:39289-95. 2004.... - Further evidence for the role of cryptochromes in retinohypothalamic photoreception/phototransductionCarol L Thompson
Department of Biochemistry and Biophysics CB 7260, School of Medicine, University of North Carolina, Chapel Hill, NC 27599 7260, USA
Brain Res Mol Brain Res 122:158-66. 2004.... - The human Rad9-Rad1-Hus1 checkpoint complex stimulates flap endonuclease 1Wensheng Wang
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
Proc Natl Acad Sci U S A 101:16762-7. 2004..This suggests that 9-1-1 is a damage-specific activator of FEN1... - Purification and characterization of three members of the photolyase/cryptochrome family blue-light photoreceptors from Vibrio choleraeErin N Worthington
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
J Biol Chem 278:39143-54. 2003..In addition, VcCry1 exhibits RNA binding activity and co-purifies with an RNA of 60-70 nucleotides in length... - DNA distress: just ring 9-1-1Michael Kemp
Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Curr Biol 19:R733-4. 2009.... - Effect of damage type on stimulation of human excision nuclease by SWI/SNF chromatin remodeling factorRyujiro Hara
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
Mol Cell Biol 23:4121-5. 2003..Equally important, we find that SWI/SNF stimulates the removal of AAF-G and (6-4) photoproduct but not of CPD from nucleosomal DNA. These results shed new light on the low rate of repair of CPDs in human cells in vivo... - Thermodynamic cooperativity and kinetic proofreading in DNA damage recognition and repairJoyce T Reardon
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7260, USA
Cell Cycle 3:141-4. 2004.... - Circadian oscillation of nucleotide excision repair in mammalian brainTae Hong Kang
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Proc Natl Acad Sci U S A 106:2864-7. 2009..The circadian oscillation of the repair capacity is caused at least in part by the circadian oscillation of the xeroderma pigmentosum A DNA damage recognition protein... - The human Rad9 checkpoint protein stimulates the carbamoyl phosphate synthetase activity of the multifunctional protein CADLaura A Lindsey-Boltz
Department of Biochemistry and Biophysics, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
Nucleic Acids Res 32:4524-30. 2004..Similar results were also obtained with an N-terminal Rad9 fragment. These findings suggest that Rad9 may play a role in ribonucleotide biosynthesis... - Purification and characterization of a type III photolyase from Caulobacter crescentusNuri Ozturk
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
Biochemistry 47:10255-61. 2008..Using enzyme preparations that contain either both chromophores or only folate, we were able to determine the efficiency and rate of transfer of energy from MTHF to FAD... - Analysis of the role of intraprotein electron transfer in photoreactivation by DNA photolyase in vivoI Halil Kavakli
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
Biochemistry 43:15103-10. 2004..We conclude that photoreduction by intraprotein electron transfer is not part of the photolyase photocycle under physiological conditions... - Role of structural plasticity in signal transduction by the cryptochrome blue-light photoreceptorCarrie L Partch
Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA
Biochemistry 44:3795-805. 2005..Collectively, these findings provide the first biochemical evidence for the proposed conformational rearrangement of cryptochromes upon light exposure... - Photolyase and cryptochrome blue-light photoreceptorsAziz Sancar
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA
Adv Protein Chem 69:73-100. 2004 - Photochemistry and photobiology of cryptochrome blue-light photopigments: the search for a photocycleCarrie L Partch
Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
Photochem Photobiol 81:1291-304. 2005..In particular, the role of the unique C-terminal domain in cryptochrome phototransduction is discussed... - Active site of (A)BC excinuclease. I. Evidence for 5' incision by UvrC through a catalytic site involving Asp399, Asp438, Asp466, and His538 residuesJ J Lin
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599
J Biol Chem 267:17688-92. 1992..Our data suggest that UvrC makes the 5' incision by employing a mechanism whereby the three carboxylates acting in concert with H538 and a Mg2+ ion facilitate nucleophilic attack by an active site water molecule... - Comparative photochemistry of animal type 1 and type 4 cryptochromesNuri Ozturk
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
Biochemistry 48:8585-93. 2009..Finally, we demonstrate that in contrast to animal type 2 CRYs and Arabidopsis CRY1 neither insect type 1 nor type 4 CRYs have autokinase activities... - An alternative form of replication protein a expressed in normal human tissues supports DNA repairMichael G Kemp
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
J Biol Chem 285:4788-97. 2010..Our findings provide the first direct evidence for the function of aRPA in human DNA metabolism and support a model for aRPA functioning in chromosome maintenance functions in nonproliferating cells... - Circadian photoreception in humans and miceIbrahim Halil Kavakli
Department Biochemistry and Biophysics Mary Ellen Jones Building, CB7260 University of North Carolina School of Medicine Chapel Hill, NC 27599, USA
Mol Interv 2:484-92. 2002..The classical photoreceptors in the outer retina, and melanopsin or other minor opsins in the inner retina, may perform redundant functions in circadian rhythmicity... - Nucleotide excision repair, oxidative damage, DNA sequence polymorphisms, and cancer treatmentStephanie Q Hutsell
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7260, USA
Clin Cancer Res 11:1355-7. 2005 - Long patch base excision repair proceeds via coordinated stimulation of the multienzyme DNA repair complexLata Balakrishnan
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
J Biol Chem 284:15158-72. 2009..Our results imply that this mechanism is still carried out, but in the context of a multienzyme complex that remains structurally intact during the repair process... - Structures of the human Rad17-replication factor C and checkpoint Rad 9-1-1 complexes visualized by glycerol spray/low voltage microscopyJack D Griffith
Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
J Biol Chem 277:15233-6. 2002..Therefore, our results demonstrate structural similarity between the checkpoint Rad complexes and the PCNA and RFC replication factors and thus provide further support for models proposing analogous functions for these complexes... - Identification and characterization of human MUS81-MMS4 structure-specific endonucleaseMüge Oğrünç
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7260, USA
J Biol Chem 278:21715-20. 2003..Using immunoaffinity purification we show that hMUS81 or hMMS4 alone have no detectable nuclease activity, but that the hMUS81.hMMS4 complex is a structure-specific nuclease that is capable of resolving fork structures... - Nucleotide excision repair in E. coli and manAziz Sancar
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Adv Protein Chem 69:43-71. 2004 - Recognition and repair of the cyclobutane thymine dimer, a major cause of skin cancers, by the human excision nucleaseJoyce T Reardon
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
Genes Dev 17:2539-51. 2003.... - Analysis of autophosphorylating kinase activities of Arabidopsis and human cryptochromesSezgin Ozgur
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
Biochemistry 45:13369-74. 2006..Finally, we find that the kinase activity of AtCry1 is not significantly affected by light or the redox status of the flavin cofactor... - Formation and function of flavin anion radical in cryptochrome 1 blue-light photoreceptor of monarch butterflySang Hun Song
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
J Biol Chem 282:17608-12. 2007....
Research Grants
- DNA Excision Repair and DNA Damage CheckpointsAziz Sancar; Fiscal Year: 2007..These studies will provide biochemical tests of current checkpoint models that are based on genetic and cellular analyses. ..
- ROLE OF CRYPTOCHROME IN DNA DAMAGE RESPONSES AND THE CIRCADIAN CLOCKAziz Sancar; Fiscal Year: 2010..We will use genetic and biochemical approaches to understand these regulatory mechanisms and establish a rational basis for chronochemotherapy. ..
- NECLEOTIDE EXCISION REPAIR ENZYMESAziz Sancar; Fiscal Year: 2003..The biochemical properties of the proteins involved in this checkpoint response will be studied and an in vitro system for the reconstitution of DNA damage checkpoint pathways will be established. ..
- NUCLEOTIDE EXCISION REPAIR ENZYMESAziz Sancar; Fiscal Year: 1993..e) The XP genes of complementation groups XP-A, -B, -C, -D, and -E will be cloned and the gene products will be overproduced, purified and characterized...
- DNA Excision Repair and DNA Damage CheckpointsAziz Sancar; Fiscal Year: 2010....
- Photolyase/cryptochrome Family, DNA Repair/Circadian ClockAziz Sancar; Fiscal Year: 2009..3. We will analyze the light-independent function of cryptochrome in the circadian clock and determine the effects of clock disruption on DNA damage checkpoints at the cellular level and on tumorigenesis in mice. ..
- Photolyase/cryptochrome Family, DNA Repair/Circadian ClockAziz Sancar; Fiscal Year: 2007..3. We will analyze the light-independent function of cryptochrome in the circadian clock and determine the effects of clock disruption on DNA damage checkpoints at the cellular level and on tumorigenesis in mice. ..
- STRUCTURE AND FUNCTION OF UVRABC EXCISION NUCLEASEAziz Sancar; Fiscal Year: 1991..coli DNA ligase. This system will be used to investigate the origin of the short and long repair patches observed in vivo and the involvement of recA protein in long patch repair...
- NUCLEOTIDE EXCISION REPAIR ENZYMESAziz Sancar; Fiscal Year: 1999....
- STRUCTURE AND FUNCTION OF DNA PHOTOLYASEAziz Sancar; Fiscal Year: 1993....
- STRUCTURE AND REGULATION OF E. COLI DNA PHOTOLYASEAziz Sancar; Fiscal Year: 1990..The regulatory sites will be investigated by in vitro and in vivo footprinting techniques...