Research Topics
| FRED PERRINOSummaryAffiliation: Wake Forest University School of Medicine Country: USA Publications
Research Grants
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Detail Information
Publications
Two functional domains of the epsilon subunit of DNA polymerase IIIF W Perrino
Wake Forest University School of Medicine, Department of Biochemistry, Winston Salem, North Carolina 27157, USA
Biochemistry 38:16001-9. 1999..These data support the concept that epsilon contains a catalytic domain located within the N-terminal region and an alpha-association domain located within the C-terminal region of the protein...
RNaseH2 mutants that cause Aicardi-Goutieres syndrome are active nucleasesFred W Perrino
Department of Biochemistry, Wake Forest University Health Sciences, Winston Salem, NC, 27157, USA
J Mol Med (Berl) 87:25-30. 2009....- Cooperative DNA binding and communication across the dimer interface in the TREX2 3' --> 5'-exonucleaseFred W Perrino
Department of Biochemistry, Wake Forest University Health Sciences, Winston Salem, NC 27157, USA
J Biol Chem 283:21441-52. 2008..A DNA binding analysis of TREX2 and the heterodimers indicates a cooperative binding effect within the TREX2 protomer. Finally, single turnover kinetic assays identify DNA binding as the rate-limiting step in TREX2 catalysis... - Polymerization past the N2-isopropylguanine and the N6-isopropyladenine DNA lesions with the translesion synthesis DNA polymerases eta and iota and the replicative DNA polymerase alphaFred W Perrino
Department of Biochemistry, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, USA
Chem Res Toxicol 18:1451-61. 2005.... - The human TREX2 3' -> 5'-exonuclease structure suggests a mechanism for efficient nonprocessive DNA catalysisFred W Perrino
Department of Biochemistry, Center for Structural Biology, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, USA
J Biol Chem 280:15212-8. 2005.... - DNA binding induces active site conformational change in the human TREX2 3'-exonucleaseUdesh de Silva
Department of Biochemistry, Wake Forest University Health Sciences, Winston Salem, NC 27157, USA
Nucleic Acids Res 37:2411-7. 2009..The structure also shows how TREX proteins potentially interact with double-stranded DNA and suggest features that might be involved in strand denaturation to provide a single-stranded substrate for the active site... - Lesion bypass of N2-ethylguanine by human DNA polymerase iotaMatthew G Pence
Department of Biochemistry and Center for Structural Biology, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, USA
J Biol Chem 284:1732-40. 2009.... - The crystal structure of TREX1 explains the 3' nucleotide specificity and reveals a polyproline II helix for protein partneringUdesh de Silva
Department of Biochemistry, Center for Structural Biology, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157
J Biol Chem 282:10537-43. 2007..The structure also reveals an 8-amino acid polyproline II helix within the TREX1 enzyme that suggests a mechanism for interactions of this exonuclease with other protein complexes... - The structure of the mammalian RNase H2 complex provides insight into RNA.NA hybrid processing to prevent immune dysfunctionNadine M Shaban
Department of Biochemistry, Center for Structural Biology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
J Biol Chem 285:3617-24. 2010.... - Sequence variants in the 3'-->5' deoxyribonuclease TREX2: identification in a genetic screen and effects on catalysis by the recombinant proteinsFred W Perrino
Department of Biochemistry, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA
Adv Enzyme Regul 44:37-49. 2004 - The N2-ethylguanine and the O6-ethyl- and O6-methylguanine lesions in DNA: contrasting responses from the "bypass" DNA polymerase eta and the replicative DNA polymerase alphaFred W Perrino
Department of Biochemistry and Department of Cancer Biology, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157, USA
Chem Res Toxicol 16:1616-23. 2003..These results suggest that accurate replication past the N(2)-ethylGua adduct might be facilitated in cells by pausing of replication catalyzed by DNA polymerase alpha and lesion bypass catalyzed by DNA polymerase eta... - The TREX1 double-stranded DNA degradation activity is defective in dominant mutations associated with autoimmune diseaseDuane A Lehtinen
Department of Biochemistry, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, USA
J Biol Chem 283:31649-56. 2008..The dysfunctional dsDNA degradation activities of these disease-related TREX1 mutants could account for persistent dsDNA from dying cells leading to an aberrant immune response in these clinically related disorders... - Dysfunctional proofreading in the Escherichia coli DNA polymerase III coreDuane A Lehtinen
Wake Forest University Health Sciences, Department of Biochemistry, Winston Salem, NC 27157, USA
Biochem J 384:337-48. 2004..Thus the epsilon511 mutant has wild-type 3'-->5' exonuclease activity and associates physically with the alpha- and theta;-subunits to generate a proofreading-defective DNA pol III enzyme... - Mutagenesis by exocyclic alkylamino purine adducts in Escherichia coliDana C Upton
Wake Forest University Health Sciences, Winston-Salem, NC, USA
Mutat Res 599:1-10. 2006..We conclude that N(2)-ethyl and -isopropyldeoxyguanosine are mutagenic adducts in E. coli whose mutation spectra differ markedly from that of O(6)-ethyldeoxyguanosine... - The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell deathDipanjan Chowdhury
CBR Institute for Biomedical Research, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA
Mol Cell 23:133-42. 2006..After granzyme A activates NM23-H1 to make single-stranded nicks, TREX1 removes nucleotides from the nicked 3' end to reduce the possibility of repair by rejoining the nicked ends... - Model for the catalytic domain of the proofreading epsilon subunit of Escherichia coli DNA polymerase III based on NMR structural dataEugene F Derose
Laboratory of Structural Biology and Laboratory of Molecular Genetics, NIEHS, Box 12233, Research Triangle Park, North Carolina 27709, USA
Biochemistry 41:94-110. 2002..Nearly all of the residues which have been identified as mutators are located in the portion of the molecule which binds the DNA, with most of these playing either a catalytic or structural role... - Elucidation of the epsilon-theta subunit interface of Escherichia coli DNA polymerase III by NMR spectroscopyEugene F Derose
Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Box 12233, Research Triangle Park, North Carolina 27709, USA
Biochemistry 42:3635-44. 2003..These chemical shift mapping results also suggest an explanation for how the unstable dnaQ49 mutator phenotype of epsilon may be stabilized by binding theta... - Structure of the Escherichia coli DNA polymerase III epsilon-HOT proofreading complexThomas W Kirby
Laboratory of Structural Biology, National Institute of Environmental Health Sciences NIH, 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA
J Biol Chem 281:38466-71. 2006..This structure provides insight into how HOT and, by implication, may stabilize the epsilon subunit, thus promoting efficient proofreading during chromosomal replication... - A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupusMin Ae Lee-Kirsch
Klinik fur Kinder und Jugendmedizin, Technische Universitat Dresden, Fetscherstr 74, 01307, Dresden, Germany
J Mol Med (Berl) 85:531-7. 2007..Our findings also warrant further investigation of TREX1 in common forms of lupus erythematosus... - Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi-Goutieres syndromeGillian Rice
Leeds Institute of Molecular Medicine, St James s University Hospital, Leeds, LS9 7TF, UK
Am J Hum Genet 80:811-5. 2007..Additionally, we describe a de novo heterozygous mutation, affecting a critical catalytic residue in TREX1, that results in typical Aicardi-Goutieres syndrome... - WRN exonuclease activity is blocked by DNA termini harboring 3' obstructive groupsJeanine A Harrigan
Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, United States
Mech Ageing Dev 128:259-66. 2007.... - Replication of N2-ethyldeoxyguanosine DNA adducts in the human embryonic kidney cell line 293Dana C Upton
Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157, USA
Chem Res Toxicol 19:960-7. 2006..Taken together, these data indicate that N(2)-ethyldGuo in DNA exerts its principal biological activity by blocking translesion DNA synthesis in human cells, resulting in either failure of replication or frameshift deletion mutations... - Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosusMin Ae Lee-Kirsch
Klinik fur Kinder und Jugendmedizin, Technische Universitat Dresden, 01307 Dresden, Germany
Nat Genet 39:1065-7. 2007..1 x 10(-7)). We demonstrate that two mutant TREX1 alleles alter subcellular targeting. Our findings implicate TREX1 in the pathogenesis of SLE...
Research Grants
- Mechanisms of the 3'-->5' deoxyribonucleasesFred W Perrino; Fiscal Year: 2010..The outcome of the proposed research will have a significant impact on the medical treatment of complex autoimmune diseases such as systemic lupus erythematosus. ..
- Mechanisms of the 3'-->5' deoxyribonucleasesFRED PERRINO; Fiscal Year: 2009..The outcome of the proposed research will have a significant impact on the medical treatment of complex autoimmune diseases such as systemic lupus erythematosus. ..
- Mechanisms of the 3'-5' deoxyribonucleasesFRED PERRINO; Fiscal Year: 2007..Identification of the TREX genes encoding these 3'-->5' deoxyribonucleases has made possible these mechanistic studies that will provide new insights into the physiological function of these enzymes. ..
- Mechanisms of the 3'-->5' deoxyribonucleasesFRED PERRINO; Fiscal Year: 2009..The outcome of the proposed research will have a significant impact on the medical treatment of complex autoimmune diseases such as systemic lupus erythematosus. ..