Research Topics
Species | M LieberSummaryAffiliation: University of Southern California Country: USA Publications
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Publications
Mechanisms of chromosomal rearrangement in the human genomeAlbert G Tsai
USC Norris Comprehensive Cancer Ctr, Rm 5428 Departments of Pathology, Biochemistry and Molecular Biology, Molecular Microbiology and Immunology, and of Biological Sciences Section of Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089 9176, USA
BMC Genomics 11:S1. 2010....
Antibody diversity: a link between switching and hypermutationM Lieber
Departments of Pathology, Biochemistry, Microbiology and Biology, University of Southern California School of Medicine, Los Angeles, California 90098, USA
Curr Biol 10:R798-800. 2000..These findings now explain cases of autosomal hyper-IgM syndrome and reveal that critical components for key functions of B cells require RNA editing...- Ageing, repetitive genomes and DNA damageMichael R Lieber
University of Southern California Norris Comprehensive Cancer Center, Room 5428, Department of Pathology, 1441 Eastlake Avenue, MC9176, Los Angeles, California 90033, USA
Nat Rev Mol Cell Biol 5:69-75. 2004..The mitochondrial production of reactive oxygen species is inversely proportional to longevity in animals. A key question now is, which molecules, among those that are oxidized, affect the lifespan of the organism most significantly?.. - Generation and characterization of endonuclease G null miceRyan A Irvine
Norris Comprehensive Cancer Center, Rm 5428, Keck School of Medicine, University of Southern California, 1441 Eastlake Ave, MC9176, Los Angeles, CA 90033, USA
Mol Cell Biol 25:294-302. 2005..The early embryonic lethality of endo G null mice recently reported by others may be due to the disruption of the gene that overlaps the endo G gene... - Mechanism and regulation of human non-homologous DNA end-joiningMichael R Lieber
Norris Comprehensive Cancer Center, Department of Pathology, University of Southern California School of Medicine, 1441 Eastlake Avenue, MS 9176, Los Angeles, California 90089, USA
Nat Rev Mol Cell Biol 4:712-20. 2003..NHEJ is typically imprecise, a characteristic that is useful for immune diversification in lymphocytes, but which might also contribute to some of the genetic changes that underlie cancer and ageing... - Roles of nonhomologous DNA end joining, V(D)J recombination, and class switch recombination in chromosomal translocationsMichael R Lieber
USC Norris Comprehensive Cancer Ctr, Rm 5428, University of Southern California, Keck School of Medicine 1441 Eastlake Ave, MC 9176 Los Angeles, CA 90089, USA
DNA Repair (Amst) 5:1234-45. 2006.... - Mechanistic basis for RAG discrimination between recombination sites and the off-target sites of human lymphomasNoriko Shimazaki
USC Norris Comprehensive Cancer Center, Departments of Pathology, Biochemistry and Molecular Biology, Molecular Microbiology and Immunology, and Biological Sciences, Section of Molecular and Computational Biology, Los Angeles, California, USA
Mol Cell Biol 32:365-75. 2012..These features explain many aspects of RAG physiology and pathophysiology... - The mechanism of human nonhomologous DNA end joiningMichael R Lieber
Norris Comprehensive Cancer Center, Department of Pathology, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089 9176, USA
J Biol Chem 283:1-5. 2008..Physiologic double-strand break processes make use of the imprecision of NHEJ in generating antigen receptor diversity. Pathologically, the imprecision of NHEJ contributes to genome mutations that arise over time... - Flexibility in the order of action and in the enzymology of the nuclease, polymerases, and ligase of vertebrate non-homologous DNA end joining: relevance to cancer, aging, and the immune systemMichael R Lieber
USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Rm 5428, Los Angeles, CA 90089 9176, USA
Cell Res 18:125-33. 2008..The loss of information locally at sites of NHEJ repair may contribute to cancer and aging, but the action by NHEJ ensures that entire segments of chromosomes are not lost... - The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathwayMichael R Lieber
Norris Comprehensive Cancer Center, Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, California 90089, USA
Annu Rev Biochem 79:181-211. 2010..Therefore, patients lacking normal NHEJ are not only sensitive to ionizing radiation (IR), but also severely immunodeficient... - The mechanism of vertebrate nonhomologous DNA end joining and its role in V(D)J recombinationMichael R Lieber
USC Norris Comprehensive Cancer Ctr, Rm 5428, University of Southern California Keck School of Medicine, Department of Pathology, Los Angeles, CA 90033, USA
DNA Repair (Amst) 3:817-26. 2004..The NHEJ pathway is needed to repair these physiologic breaks, as well as challenging pathologic breaks that arise from ionizing radiation and oxidative damage to DNA... - Nonhomologous DNA end joining (NHEJ) and chromosomal translocations in humansMichael R Lieber
USC Norris Comprehensive Cancer Center, Los Angeles, CA 90089 9176, USA
Subcell Biochem 50:279-96. 2010..The causes of DSBs in lymphomas most often involve the RAG or AID enzymes that function in the specialized processes of antigen receptor gene rearrangement... - Repair of double-strand DNA breaks by the human nonhomologous DNA end joining pathway: the iterative processing modelYunmei Ma
Norris Comprehensive Cancer Center, Department of Pathology, University of Southern California, Keck School of Medicine, Los Angeles, California, USA
Cell Cycle 4:1193-200. 2005.... - Oxygen metabolism causes chromosome breaks and is associated with the neuronal apoptosis observed in DNA double-strand break repair mutantsZarir E Karanjawala
Department of Pathology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles 90089-9176, USA
Curr Biol 12:397-402. 2002..Therefore, oxygen metabolism is a major source of the genomic instability observed in NHEJ-deficient cells and, presumably, in all cells... - Hybrid joint formation in human V(D)J recombination requires nonhomologous DNA end joiningSathees C Raghavan
USC Norris Comprehensive Cancer Center Room 5428, Department of Pathology, Biochemistry and Molecular Biology, University of Southern California, Keck School of Medicine, 1441 Eastlake Avenue, MC9176, Los Angeles, CA 90033, USA
DNA Repair (Amst) 5:278-85. 2006..We find that all hybrids in vivo require DNA ligase IV in human cells, which is the final component of the NHEJ pathway. Hence, hybrid joints rely on NHEJ rather than on the RAG complex for joining... - A biochemically defined system for mammalian nonhomologous DNA end joiningYunmei Ma
University of Southern California Norris Comprehensive Cancer Center, Room 5428, Department of Pathology, University of Southern California Keck School, of Medicine, 1441 Eastlake Avenue, MC9176, Los Angeles, California 90033, USA
Mol Cell 16:701-13. 2004..The XRCC4:DNA ligase IV complex is able to ligate one strand that has only minimal base pairing with the antiparallel strand. This important aspect of the ligation leads to an iterative strand-processing model for the steps of NHEJ... - A non-B-DNA structure at the Bcl-2 major breakpoint region is cleaved by the RAG complexSathees C Raghavan
Norris Comprehensive Cancer Center, Room 5428, University of Southern California Keck School of Medicine, 1441 Eastlake Ave, MC9176, Los Angeles, California 90033, USA
Nature 428:88-93. 2004..Hence, a stable non-B-DNA structure in the human genome appears to be the basis for the fragility of the Bcl-2 Mbr, and the RAG complex is able to cleave this structure... - Analysis of the kinetic and equilibrium binding of Ku protein to DNAAlexander Taghva
Department of Pathology, Norris Comprehensive Cancer Center, University of Southern California, Rm. 5428, Los Angeles, CA 90089, USA
J Theor Biol 214:85-97. 2002..The model obtains a best fit with Ku having a roughly seven-fold preference to bind to DNA ends rather than internal positions and is consistent with Ku having a strong preference of which face of the protein loads onto the DNA end... - Double-strand break formation by the RAG complex at the bcl-2 major breakpoint region and at other non-B DNA structures in vitroSathees C Raghavan
Norris Comprehensive Cancer Center, Rm. 5428, University of Southern California Keck School of Medicine, 1441 Eastlake Ave, MC9176, Los Angeles, California 90033, USA
Mol Cell Biol 25:5904-19. 2005..Hence, the present study reveals novel insight into a third mechanism of action of RAGs on DNA, besides the standard heptamer/nonamer-mediated cleavage in V(D)J recombination and the in vitro transposase activity... 
Turning anti-ageing genes against cancerValter D Longo
Andrus Gerontology Center, Molecular and Computational Biology Department, University of Southern California, 3715 McClintock Avenue, Los Angeles, California 90089 0191, USA
Nat Rev Mol Cell Biol 9:903-10. 2008..This raises the possibility that cancer can be reduced by chronic downregulation of pro-ageing pathways...- The embryonic lethality in DNA ligase IV-deficient mice is rescued by deletion of Ku: implications for unifying the heterogeneous phenotypes of NHEJ mutantsZarir E Karanjawala
Norris Comprehensive Cancer Center, Rm 5428, Department of Pathology, University of Southern California, Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA
DNA Repair (Amst) 1:1017-26. 2002.... - DNA structures at chromosomal translocation sitesSathees C Raghavan
Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
Bioessays 28:480-94. 2006..Here we summarize these findings and integrate them with other recent data for non-B structures at sites of consistent constitutional chromosomal translocations... - The cleavage efficiency of the human immunoglobulin heavy chain VH elements by the RAG complex: implications for the immune repertoireKefei Yu
Norris Comprehensive Cancer Center, Department of Pathology, University of Southern California, Keck School of Medicine, Los Angeles, California 90089-9176, USA
J Biol Chem 277:5040-6. 2002..This correspondence raises the possibility that the dominant factor determining V(H) element utilization within the 1-megabase human genomic V(H) array is simply the individual RAG cleavage efficiencies... - Kinetic analysis of the nicking and hairpin formation steps in V(D)J recombinationKefei Yu
Department of Pathology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Room 5428, 1441 Eastlake Avenue, MC 9176, Los Angeles, CA 90033, USA
DNA Repair (Amst) 3:67-75. 2004..The physiologic implications of this and other kinetic inferences of these time courses are discussed... - Downstream boundary of chromosomal R-loops at murine switch regions: implications for the mechanism of class switch recombinationFeng-Ting Huang
Department of Pathology, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, MC9176, Los Angeles, CA 90089-9176, USA
Proc Natl Acad Sci U S A 103:5030-5. 2006..The implications of these findings are discussed in the context of models for the targeting of class switch recombination... 
Single-stranded DNA ligation and XLF-stimulated incompatible DNA end ligation by the XRCC4-DNA ligase IV complex: influence of terminal DNA sequenceJiafeng Gu
Department of Pathology, Biochemistry and Molecular Biology, Biological Sciences, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA, USA
Nucleic Acids Res 35:5755-62. 2007..The dT preference of the ligase is interesting given the sequence bias of the NHEJ polymerase. These distinctive properties of the XRCC4-DNA ligase IV complex explain important aspects of its in vivo roles...- The DNA-dependent protein kinase catalytic subunit phosphorylation sites in human ArtemisYunmei Ma
Department of Pathology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90089 9176, USA
J Biol Chem 280:33839-46. 2005..Therefore, the C-terminal domain may have a negative regulatory effect on the Artemis endonucleolytic activities, and phosphorylation by DNA-PKcs in the C-terminal domain may relieve this inhibition... - Both V(D)J coding ends but neither signal end can recombine at the bcl-2 major breakpoint region, and the rejoining is ligase IV dependentSathees C Raghavan
USC Norris Comprehensive Cancer Ctr, Rm. 5428, 1441 Eastlake Ave, Los Angeles, CA 90089-9176, USA
Mol Cell Biol 25:6475-84. 2005..These results permit us to formulate a complete model for the order and types of cleavage and rejoining events in the t(14;18) translocation... - XRCC4:DNA ligase IV can ligate incompatible DNA ends and can ligate across gapsJiafeng Gu
Department of Pathology, Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
EMBO J 26:1010-23. 2007..These observations provide an explanation for several in vivo observations that were difficult to understand previously... - The Artemis:DNA-PKcs endonuclease cleaves DNA loops, flaps, and gapsYunmei Ma
Department of Pathology, Norris Comprehensive Cancer Center, Rm 5428, University of Southern California Keck School of Medicine, Los Angeles, CA 90089 9176, USA
DNA Repair (Amst) 4:845-51. 2005..Additionally, the flexibility of the Artemis:DNA-PKcs nuclease may be important in removing secondary structures that hinder processing of DNA ends during NHEJ... - Evidence for a triplex DNA conformation at the bcl-2 major breakpoint region of the t(14;18) translocationSathees C Raghavan
Norris Comprehensive Cancer Center, Zilka Neurogenetics Institute, University of Southern California Keck School of Medicine, Los Angeles, 90033, USA
J Biol Chem 280:22749-60. 2005..We infer that an imperfect purine/purine/pyrimidine (R.R.Y) triplex likely forms at the bcl-2 Mbr in vitro, and in vivo recombination data favor this as the major DNA conformation in vivo as well... - H3K4me3 stimulates the V(D)J RAG complex for both nicking and hairpinning in trans in addition to tethering in cis: implications for translocationsNoriko Shimazaki
Department of Pathology, University of Southern California Norris Comprehensive Center, Room 5428, 1441 Eastlake Avenue, MC 9176, Los Angeles, CA 90089 9176, USA
Mol Cell 34:535-44. 2009..The H3K4me3 catalytic stimulation applies to suboptimal cryptic RSS sites located at H3K4me3 peaks that are critical in the inception of human T cell acute lymphoblastic lymphomas... - DNA damage and agingZarir E Karanjawala
Department of Pathology, USC Norris Comprehensive Center, Los Angeles, CA 90033, USA
Mech Ageing Dev 125:405-16. 2004..Repetitive DNA content may determine the extent to which any organism can use this pathway, and therefore, may dictate a key factor in the balance between oxidation and organismal lifespan... - Conformational variants of duplex DNA correlated with cytosine-rich chromosomal fragile sitesAlbert G Tsai
Department of Biochemistry, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90089 9176, USA
J Biol Chem 284:7157-64. 2009..These characteristics of homo-C tracts in duplex DNA may be associated with DNA-protein interactions in vivo that predispose certain genomic regions to chromosomal fragility... - Overexpression of Cu/Zn superoxide dismutase is lethal for mice lacking double-strand break repairZarir E Karanjawala
Department of Pathology, USC Norris Comprehensive Cancer Center, Rm 5428, Keck School of Medicine, University of Southern California, 1441 Eastlake Ave, MC9176, Los Angeles, CA 90089 9176, USA
DNA Repair (Amst) 2:285-94. 2003..Based on these results, we propose a model in which oxidative metabolism causes chromosome breaks, leading to neuronal death; and this neuronal death may account for that seen in NHEJ mutant animals and in mammals with SOD1-mediated ALS... - Length-dependent binding of human XLF to DNA and stimulation of XRCC4.DNA ligase IV activityHaihui Lu
Department of Pathology, Norris Comprehensive Cancer Center, Los Angeles, California 90089 9176, USA
J Biol Chem 282:11155-62. 2007..Surprisingly, the mutant protein retained its ability to stimulate XRCC4.DNA ligase IV but failed to translocate to the nucleus, and this appears to be the basis for the NHEJ defect in this patient... - Sequence dependence of chromosomal R-loops at the immunoglobulin heavy-chain Smu class switch regionFeng Ting Huang
Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, California 90089 9176, USA
Mol Cell Biol 27:5921-32. 2007..These studies also provide the first analysis of how R-loop formation in the eukaryotic chromosome depends on the DNA sequence... - Binding of inositol hexakisphosphate (IP6) to Ku but not to DNA-PKcsYunmei Ma
Norris Comprehensive Cancer Center, Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, California 90089 9176, USA
J Biol Chem 277:10756-9. 2002..Furthermore, the binding of DNA ends and IP(6) to Ku are independent of each other. The possible relationship between inositol phosphate metabolism and DNA repair is discussed in light of these findings... - DNA-PKcs regulates a single-stranded DNA endonuclease activity of ArtemisJiafeng Gu
Department of Pathology, Norris Comprehensive Cancer Center, Los Angeles, CA 90089, USA
DNA Repair (Amst) 9:429-37. 2010..These findings further expand the range of DNA substrates upon which Artemis and Artemis:DNA-PKcs can act. The findings are discussed in the context of NHEJ... - Extent to which hairpin opening by the Artemis:DNA-PKcs complex can contribute to junctional diversity in V(D)J recombinationHaihui Lu
Department of Pathology, Norris Comprehensive Cancer Center, Los Angeles, CA, USA
Nucleic Acids Res 35:6917-23. 2007..This information provides greater clarity on the extent to which the hairpin opening position contributes to junctional diversification in V(D)J recombination... - Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombinationYunmei Ma
Norris Comprehensive Cancer Center, Rm 5428, Departments of Biochemistry and Molecular Biology, Pathology, Biological Sciences, and Molecular Microbiology and Immunology, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA
Cell 108:781-94. 2002.... - Two overlapping divergent transcription units in the human genome: the FEN1/C11orf10 locusNoritaka Adachi
Norris Comprehensive Cancer Center, Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA
OMICS 6:273-9. 2002..Importantly, in the human genome, the two mRNAs are overlapping (14 bp) in their 5' ends. Thus, the FEN1/C11orf10 locus is a new example of two overlapping, divergent transcription units in the human genome... - R-loops at immunoglobulin class switch regions in the chromosomes of stimulated B cellsKefei Yu
USC Norris Comprehensive Cancer Center, Room 5428, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, MC 9176, Los Angeles, CA 90033, USA
Nat Immunol 4:442-51. 2003..The length of the R-loops can exceed 1 kilobase. We propose that this distinctive DNA structure is important in the class switch recombination mechanism.. - Chromosomal translocations and non-B DNA structures in the human genomeSathees C Raghavan
Norris Comprehensive Cancer Center, Department of Pathology, University of Southern California, Keck School of Medicine, Los Angeles, California 90033, USA
Cell Cycle 3:762-8. 2004..Recent progress on the most common translocation in human cancer, t(14;18), highlights interesting issues in DNA structure and in the enzymes involved in the cutting and joining phases of the process... - Nucleic acid structures and enzymes in the immunoglobulin class switch recombination mechanismKefei Yu
Department of Pathology, Norris Comprehensive Cancer Ctr, Rm 5428, 1441 Eastlake Ave, MC9176, Los Angeles, CA 90033, USA
DNA Repair (Amst) 2:1163-74. 2003..Progress has been made on the enzymes involved in leading to the DNA cleavage events and on identifying the unusual DNA structures that those enzymes recognize... - In vitro nonhomologous DNA end joining systemYunmei Ma
Department of Pathology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, USA
Methods Enzymol 408:502-10. 2006..This in vitro system allows further understanding of the biochemical features of the pathway and evaluation of the functions of other proteins in NHEJ... - A biochemically defined system for coding joint formation in V(D)J recombinationHaihui Lu
Norris Comprehensive Cancer Center, Room 5428, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, MC9176, Los Angeles, CA 90089, USA
Mol Cell 31:485-97. 2008.... - Developmental retinal apoptosis in Ku86-/- miceZarir E Karanjawala
Norris Comprehensive Cancer Center, Room 5428, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089 9176, USA
DNA Repair (Amst) 2:1429-34. 2003..This analysis of the retina provides the first opportunity to formally test the hypothesis that embryonic apoptosis accounts for reduced total cell numbers in adult Ku86-/- mice... - Mechanistic flexibility as a conserved theme across 3 billion years of nonhomologous DNA end-joiningJiafeng Gu
University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90089, USA
Genes Dev 22:411-5. 2008 - The polymerases for V(D)J recombinationMichael R Lieber
USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, 90089-9176, USA
Immunity 25:7-9. 2006..V(D)J recombination is no exception. In this issue, Bertocci et al. (2006) have provided new insight by generating mice deficient in one or more of the polymerases... - FACT-mediated exchange of histone variant H2AX regulated by phosphorylation of H2AX and ADP-ribosylation of Spt16Kyu Heo
Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA
Mol Cell 30:86-97. 2008..Thus, these data establish FACT as the major regulator involved in H2AX exchange process that is modulated by H2AX phosphorylation and Spt16 ADP-ribosylation... - Human chromosomal translocations at CpG sites and a theoretical basis for their lineage and stage specificityAlbert G Tsai
Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, MC9176, Los Angeles, CA 90089 9176, USA
Cell 135:1130-42. 2008.... - G clustering is important for the initiation of transcription-induced R-loops in vitro, whereas high G density without clustering is sufficient thereafterDeepankar Roy
Department of Pathology, Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, Los Angeles, CA 90089 9176, USA
Mol Cell Biol 29:3124-33. 2009..Without both a favorable R-loop initiation zone and elongation zone, R-loop formation is inefficient... - The B cell mutator AID promotes B lymphoid blast crisis and drug resistance in chronic myeloid leukemiaLars Klemm
Leukemia and Lymphoma Program, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90027, USA
Cancer Cell 16:232-45. 2009..Importantly, our data uncover a causative role of AID activity in the acquisition of BCR-ABL1 mutations leading to Imatinib resistance, thus providing a rationale for the rapid development of drug resistance and blast crisis progression... - Competition between the RNA transcript and the nontemplate DNA strand during R-loop formation in vitro: a nick can serve as a strong R-loop initiation siteDeepankar Roy
Department of Pathology, USC Norris Comprehensive Cancer Center, Los Angeles, CA 90089 9176, USA
Mol Cell Biol 30:146-59. 2010..This has important implications for class switch recombination and somatic hypermutation and possibly for other biological processes in transcribed regions... - Stability and strand asymmetry in the non-B DNA structure at the bcl-2 major breakpoint regionSathees C Raghavan
Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
J Biol Chem 279:46213-25. 2004..These findings place major constraints on the location and nature of the non-B conformations assumed at peaks I and III of the bcl-2 Mbr... - Analysis of non-B DNA structure at chromosomal sites in the mammalian genomeSathees C Raghavan
Department of Pathology, University of Southern California, Keck School of Medicine, Los Angeles, USA
Methods Enzymol 409:301-16. 2006..This is a powerful assay because it provides information on individual DNA molecules. The second approach uses preexisting DNA structural reagents, but describes our specific application of them to analysis of DNA in vivo... - Mechanism of R-loop formation at immunoglobulin class switch sequencesDeepankar Roy
USC Norris Comprehensive Cancer Ctr, Rm 5428, 1441 Eastlake Ave, MC9176, Los Angeles, CA 90089 9176, USA
Mol Cell Biol 28:50-60. 2008..This provides an independent basis for concluding that the primary function of G clustering, in the context of high G density, is R-loop formation... - Detection and structural analysis of R-loopsKefei Yu
Department of Pathology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, USA
Methods Enzymol 409:316-29. 2006..Our own lab has focused on class switch regions, where the R-loops can extend well over a kilobase in length. Here, methods are described for detection and analysis of R-loops in vitro and in vivo... - DNA substrate length and surrounding sequence affect the activation-induced deaminase activity at cytidineKefei Yu
University of Southern California Norris Comprehensive Cancer Center, Department of Pathology, Los Angeles, California 90089, USA
J Biol Chem 279:6496-500. 2004..AID preferentially deaminates Cs in the WRC motif, and additionally has a small but consistent preference for purine at the position after the WRC, thereby favoring WRCr (the lowercase r corresponds to the smaller impact on activity)... - The structure-specific nicking of small heteroduplexes by the RAG complex: implications for lymphoid chromosomal translocationsSathees C Raghavan
Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India
DNA Repair (Amst) 6:751-9. 2007..We consider these findings in the context of RAG nicking at non-B DNA structures in lymphoid chromosomal translocations... - Functional and biochemical dissection of the structure-specific nuclease ARTEMISUlrich Pannicke
Institute for Clinical Transfusion Medicine and Immunogenetics, and Department of Transfusion Medicine, University of Ulm, Ulm, Germany
EMBO J 23:1987-97. 2004..These results indicate that the hairpin-opening activity of ARTEMIS and/or its overhang endonucleolytic activity are necessary but its exonuclease activity is not sufficient for the process of V(D)J recombination... - Human severe combined immune deficiency and DNA repairKlaus Schwarz
Department of Transfusion Medicine, University of Ulm, Germany
Bioessays 25:1061-70. 2003.... - DNA-PKcs dependence of Artemis endonucleolytic activity, differences between hairpins and 5' or 3' overhangsDoris Niewolik
Institute for Clinical Transfusion Medicine and Immunogenetics and the Department of Transfusion Medicine, the University Hospital Ulm, D-89081 Ulm, Germany
J Biol Chem 281:33900-9. 2006..Second, DNA-PKcs may optimally configure 5' and 3' overhang substrates for the endonucleolytic function of Artemis... - Genetic interactions between BLM and DNA ligase IV in human cellsSairei So
Kihara Institute for Biological Research, Graduate School of Integrated Science, Yokohama City University, Maioka cho 641 12, Totsuka ku, Yokohama 244 0813, Japan
J Biol Chem 279:55433-42. 2004..Collectively, our results provide the first evidence for genetic interactions between BLM and NHEJ in human cells... - Impact of DNA ligase IV on the fidelity of end joining in human cellsJulianne Smith
UMR 218 CNRS, Institut Curie Recherche, 26 Rue d Ulm, 75248 Paris, France
Nucleic Acids Res 31:2157-67. 2003..Thus, the ability of DNA ligase IV-XRCC4 to protect DNA ends may contribute to the ability of DNA ligase IV to promote accurate rejoining in vivo... - Prevalent involvement of illegitimate V(D)J recombination in chromosome 9p21 deletions in lymphoid leukemiaYukiko Kitagawa
Biology Division, National Cancer Center Research Institute, Tokyo 1040045, Japan
J Biol Chem 277:46289-97. 2002..These results indicated that illegitimate V(D)J recombination, which was targeted at several ectopic recombination signal sequences widely distributed in 9p21, caused a large fraction of 9p21 deletions in lymphoid leukemia... - DNA structure and human diseasesSathees C Raghavan
Department of Biochemistry, Indian Institute of Science, Bangalore, India
Front Biosci 12:4402-8. 2007..In this review, we summarize the current literature on non-B DNA structures, and discuss their role in genomic instability and diseases... - Severe combined immunodeficiency and microcephaly in siblings with hypomorphic mutations in DNA ligase IVDietke Buck
INSERM, , U429, , Paris, France
Eur J Immunol 36:224-35. 2006..These observations contrast with the severity of the clinical immunodeficiency, suggesting that Lig4 may have additional critical roles in lymphocyte survival beyond V(D)J recombination... - Omenn syndrome due to ARTEMIS mutationsMarkus Ege
Department of Transfusion Medicine, University Children s Hospital, University Hospital Ulm, Helmholtzstrasse 10, D 89081 Ulm, Germany
Blood 105:4179-86. 2005.... - Bidirectional gene organization: a common architectural feature of the human genomeNoritaka Adachi
Cell 109:807-9. 2002 - DNA-PKcs at 7 angstrom: insights for DNA repairNoriko Shimazaki
Structure 16:334-6. 2008
Research Grants
- Mechanism and Regulation of Nonhomologous DNA End JoiningMichael R Lieber; Fiscal Year: 2010..The benefits of some chemotherapy and therapeutic radiation work can be increased by this deeper level of understanding of this key DNA repair pathway. ..
- HUMAN V(D)J RECOMBINASE IN NEOPLASTIC AND PRIMARY CELLSMichael Lieber; Fiscal Year: 2004..Corresponding studies of such regions on minichromosomes will permit the testing of the effects of the direction of DNA replication and transcription. ..
- MECHANISM OF DNA RECOMBINATION AT CLASS SWITCH SEQUENCESMichael Lieber; Fiscal Year: 2005..Hence, this proposal tests in vivo substrate structure, its mechanism of formation, the action of AID enzyme on that structure, and the pathway for rejoining the ends after breakage has occurred. ..
- NORMAL AND MUTANT LYMPHOID V(D)J RECOMBINASEMichael Lieber; Fiscal Year: 2007..In the long-term, all of these studies will help establish optimal therapy for many human SCID patients and to understand the human immune repertoire. ..
- MECHANISM AND REGULATION OF NONHOMOLOGOUS DNA ENDJOININGMichael Lieber; Fiscal Year: 2007..The long-term medical benefit of a biochemically-defined NHEJ system includes the ability to test small molecule drug inhibitors for roles in cancer therapy. ..
- MECHANISMS OF HUMAN LYMPHOID CHROMOSOMAL TRANSLOCATIONMichael Lieber; Fiscal Year: 2007..Aims 1 through 4 will advance our understanding of chromosomal fragile sites in a general way because the DNA structural principles are likely to apply to other chromosomal fragile sites. ..
- MECHANISM OF DNA RECOMBINATION AT CLASS SWITCH SEQUENCESMichael Lieber; Fiscal Year: 2009..Hence, this proposal tests in vivo substrate structure, its mechanism of formation, the action of AID enzyme on that structure, and the pathway for rejoining the ends after breakage has occurred. ..
- NORMAL AND MUTANT LYMPHOID V(D)J RECOMBINASEMichael Lieber; Fiscal Year: 2009..In the long-term, all of these studies will help establish optimal therapy for many human SCID patients and to understand the human immune repertoire. ..
- MECHANISM OF DNA RECOMBINATION AT CLASS SWITCH SEQUENCESMichael R Lieber; Fiscal Year: 2010..Hence, this proposal tests in vivo substrate structure, its mechanism of formation, the action of AID enzyme on that structure, and the pathway for rejoining the ends after breakage has occurred. ..
- NORMAL AND MUTANT LYMPHOID V(D)J RECOMBINASEMichael R Lieber; Fiscal Year: 2010..In the long-term, all of these studies will help establish optimal therapy for many human SCID patients and to understand the human immune repertoire. ..
- NORMAL AND MUTANT LYMPHOID V(D)J RECOMBINASEMichael Lieber; Fiscal Year: 2004..Aim 5 utilizes all of these assays to understand human SCID defects due to V(D)J recombination. Aim 6 is directed at continuing our earlier work on chromatin effects on V(D)J recombination. ..
- HUMAN V(D)J RECOMBINASE IN NEOPLASTIC AND PRIMARY CELLSMichael Lieber; Fiscal Year: 1999....
- NORMAL AND MUTANT LYMPHOID VDJ RECOMBINASEMichael Lieber; Fiscal Year: 1999..Based on these studies and related studies of others in this field, the long-term goal is a biochemical understanding of the catalytic components of the recombinase, the steps of the reaction, and the basis for locus accessibility. ..
- MECHANISM OF DNA RECOMBINATION AT CLASS SWITCH SEQUENCESMichael Lieber; Fiscal Year: 2001..Fifth, we search for enzymatic activities in extracts that carry out the cleavage step in class switch recombination. ..