M Lieber

Summary

Affiliation: University of Southern California
Country: USA

Publications

  1. pmc Mechanisms of chromosomal rearrangement in the human genome
    Albert 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
  2. ncbi request reprint Antibody diversity: a link between switching and hypermutation
    M 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
  3. ncbi request reprint Ageing, repetitive genomes and DNA damage
    Michael 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
  4. pmc Generation and characterization of endonuclease G null mice
    Ryan 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
  5. ncbi request reprint Mechanism and regulation of human non-homologous DNA end-joining
    Michael 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
  6. ncbi request reprint Roles of nonhomologous DNA end joining, V(D)J recombination, and class switch recombination in chromosomal translocations
    Michael 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
  7. pmc Mechanistic basis for RAG discrimination between recombination sites and the off-target sites of human lymphomas
    Noriko 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
  8. ncbi request reprint The mechanism of human nonhomologous DNA end joining
    Michael 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
  9. ncbi request reprint 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 system
    Michael 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
  10. pmc The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway
    Michael 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

Research Grants

Collaborators

Detail Information

Publications72

  1. pmc Mechanisms of chromosomal rearrangement in the human genome
    Albert 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
    ....
  2. ncbi request reprint Antibody diversity: a link between switching and hypermutation
    M 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...
  3. ncbi request reprint Ageing, repetitive genomes and DNA damage
    Michael 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?..
  4. pmc Generation and characterization of endonuclease G null mice
    Ryan 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...
  5. ncbi request reprint Mechanism and regulation of human non-homologous DNA end-joining
    Michael 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...
  6. ncbi request reprint Roles of nonhomologous DNA end joining, V(D)J recombination, and class switch recombination in chromosomal translocations
    Michael 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
    ....
  7. pmc Mechanistic basis for RAG discrimination between recombination sites and the off-target sites of human lymphomas
    Noriko 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...
  8. ncbi request reprint The mechanism of human nonhomologous DNA end joining
    Michael 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...
  9. ncbi request reprint 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 system
    Michael 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...
  10. pmc The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway
    Michael 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...
  11. ncbi request reprint The mechanism of vertebrate nonhomologous DNA end joining and its role in V(D)J recombination
    Michael 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...
  12. pmc Nonhomologous DNA end joining (NHEJ) and chromosomal translocations in humans
    Michael 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...
  13. ncbi request reprint Repair of double-strand DNA breaks by the human nonhomologous DNA end joining pathway: the iterative processing model
    Yunmei 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
    ....
  14. ncbi request reprint Oxygen metabolism causes chromosome breaks and is associated with the neuronal apoptosis observed in DNA double-strand break repair mutants
    Zarir 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...
  15. ncbi request reprint Hybrid joint formation in human V(D)J recombination requires nonhomologous DNA end joining
    Sathees 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...
  16. ncbi request reprint A biochemically defined system for mammalian nonhomologous DNA end joining
    Yunmei 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...
  17. ncbi request reprint A non-B-DNA structure at the Bcl-2 major breakpoint region is cleaved by the RAG complex
    Sathees 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...
  18. ncbi request reprint Analysis of the kinetic and equilibrium binding of Ku protein to DNA
    Alexander 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...
  19. pmc Double-strand break formation by the RAG complex at the bcl-2 major breakpoint region and at other non-B DNA structures in vitro
    Sathees 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...
  20. doi request reprint Turning anti-ageing genes against cancer
    Valter 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...
  21. ncbi request reprint The embryonic lethality in DNA ligase IV-deficient mice is rescued by deletion of Ku: implications for unifying the heterogeneous phenotypes of NHEJ mutants
    Zarir 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
    ....
  22. ncbi request reprint DNA structures at chromosomal translocation sites
    Sathees 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...
  23. ncbi request reprint The cleavage efficiency of the human immunoglobulin heavy chain VH elements by the RAG complex: implications for the immune repertoire
    Kefei 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...
  24. ncbi request reprint Kinetic analysis of the nicking and hairpin formation steps in V(D)J recombination
    Kefei 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...
  25. pmc Downstream boundary of chromosomal R-loops at murine switch regions: implications for the mechanism of class switch recombination
    Feng 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...
  26. pmc Single-stranded DNA ligation and XLF-stimulated incompatible DNA end ligation by the XRCC4-DNA ligase IV complex: influence of terminal DNA sequence
    Jiafeng 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...
  27. ncbi request reprint The DNA-dependent protein kinase catalytic subunit phosphorylation sites in human Artemis
    Yunmei 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...
  28. pmc 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 dependent
    Sathees 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...
  29. pmc XRCC4:DNA ligase IV can ligate incompatible DNA ends and can ligate across gaps
    Jiafeng 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...
  30. ncbi request reprint The Artemis:DNA-PKcs endonuclease cleaves DNA loops, flaps, and gaps
    Yunmei 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...
  31. ncbi request reprint Evidence for a triplex DNA conformation at the bcl-2 major breakpoint region of the t(14;18) translocation
    Sathees 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...
  32. pmc H3K4me3 stimulates the V(D)J RAG complex for both nicking and hairpinning in trans in addition to tethering in cis: implications for translocations
    Noriko 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...
  33. ncbi request reprint DNA damage and aging
    Zarir 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...
  34. pmc Conformational variants of duplex DNA correlated with cytosine-rich chromosomal fragile sites
    Albert 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...
  35. ncbi request reprint Overexpression of Cu/Zn superoxide dismutase is lethal for mice lacking double-strand break repair
    Zarir 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...
  36. ncbi request reprint Length-dependent binding of human XLF to DNA and stimulation of XRCC4.DNA ligase IV activity
    Haihui 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...
  37. pmc Sequence dependence of chromosomal R-loops at the immunoglobulin heavy-chain Smu class switch region
    Feng 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...
  38. ncbi request reprint Binding of inositol hexakisphosphate (IP6) to Ku but not to DNA-PKcs
    Yunmei 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...
  39. pmc DNA-PKcs regulates a single-stranded DNA endonuclease activity of Artemis
    Jiafeng 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...
  40. pmc Extent to which hairpin opening by the Artemis:DNA-PKcs complex can contribute to junctional diversity in V(D)J recombination
    Haihui 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...
  41. ncbi request reprint Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination
    Yunmei 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
    ....
  42. ncbi request reprint Two overlapping divergent transcription units in the human genome: the FEN1/C11orf10 locus
    Noritaka 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...
  43. ncbi request reprint R-loops at immunoglobulin class switch regions in the chromosomes of stimulated B cells
    Kefei 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..
  44. ncbi request reprint Chromosomal translocations and non-B DNA structures in the human genome
    Sathees 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...
  45. ncbi request reprint Nucleic acid structures and enzymes in the immunoglobulin class switch recombination mechanism
    Kefei 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...
  46. ncbi request reprint In vitro nonhomologous DNA end joining system
    Yunmei 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...
  47. pmc A biochemically defined system for coding joint formation in V(D)J recombination
    Haihui 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
    ....
  48. ncbi request reprint Developmental retinal apoptosis in Ku86-/- mice
    Zarir 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...
  49. pmc Mechanistic flexibility as a conserved theme across 3 billion years of nonhomologous DNA end-joining
    Jiafeng Gu
    University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90089, USA
    Genes Dev 22:411-5. 2008
  50. ncbi request reprint The polymerases for V(D)J recombination
    Michael 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...
  51. doi request reprint FACT-mediated exchange of histone variant H2AX regulated by phosphorylation of H2AX and ADP-ribosylation of Spt16
    Kyu 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...
  52. pmc Human chromosomal translocations at CpG sites and a theoretical basis for their lineage and stage specificity
    Albert 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
    ....
  53. pmc G clustering is important for the initiation of transcription-induced R-loops in vitro, whereas high G density without clustering is sufficient thereafter
    Deepankar 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...
  54. pmc The B cell mutator AID promotes B lymphoid blast crisis and drug resistance in chronic myeloid leukemia
    Lars 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...
  55. pmc 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 site
    Deepankar 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...
  56. ncbi request reprint Stability and strand asymmetry in the non-B DNA structure at the bcl-2 major breakpoint region
    Sathees 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...
  57. ncbi request reprint Analysis of non-B DNA structure at chromosomal sites in the mammalian genome
    Sathees 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...
  58. pmc Mechanism of R-loop formation at immunoglobulin class switch sequences
    Deepankar 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...
  59. ncbi request reprint Detection and structural analysis of R-loops
    Kefei 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...
  60. ncbi request reprint DNA substrate length and surrounding sequence affect the activation-induced deaminase activity at cytidine
    Kefei 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)...
  61. pmc The structure-specific nicking of small heteroduplexes by the RAG complex: implications for lymphoid chromosomal translocations
    Sathees 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...
  62. pmc Functional and biochemical dissection of the structure-specific nuclease ARTEMIS
    Ulrich 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...
  63. ncbi request reprint Human severe combined immune deficiency and DNA repair
    Klaus Schwarz
    Department of Transfusion Medicine, University of Ulm, Germany
    Bioessays 25:1061-70. 2003
    ....
  64. ncbi request reprint DNA-PKcs dependence of Artemis endonucleolytic activity, differences between hairpins and 5' or 3' overhangs
    Doris 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...
  65. ncbi request reprint Genetic interactions between BLM and DNA ligase IV in human cells
    Sairei 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...
  66. pmc Impact of DNA ligase IV on the fidelity of end joining in human cells
    Julianne 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...
  67. ncbi request reprint Prevalent involvement of illegitimate V(D)J recombination in chromosome 9p21 deletions in lymphoid leukemia
    Yukiko 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...
  68. ncbi request reprint DNA structure and human diseases
    Sathees 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...
  69. ncbi request reprint Severe combined immunodeficiency and microcephaly in siblings with hypomorphic mutations in DNA ligase IV
    Dietke Buck
    INSERM, Hopital Necker Enfants Malades, U429, Unité Développement Normal et Pathologique du Système Immunitaire, 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...
  70. ncbi request reprint Omenn syndrome due to ARTEMIS mutations
    Markus Ege
    Department of Transfusion Medicine, University Children s Hospital, University Hospital Ulm, Helmholtzstrasse 10, D 89081 Ulm, Germany
    Blood 105:4179-86. 2005
    ....
  71. ncbi request reprint Bidirectional gene organization: a common architectural feature of the human genome
    Noritaka Adachi
    Cell 109:807-9. 2002
  72. doi request reprint DNA-PKcs at 7 angstrom: insights for DNA repair
    Noriko Shimazaki
    Structure 16:334-6. 2008

Research Grants32

  1. Mechanism and Regulation of Nonhomologous DNA End Joining
    Michael 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. ..
  2. HUMAN V(D)J RECOMBINASE IN NEOPLASTIC AND PRIMARY CELLS
    Michael 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. ..
  3. MECHANISM OF DNA RECOMBINATION AT CLASS SWITCH SEQUENCES
    Michael 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. ..
  4. NORMAL AND MUTANT LYMPHOID V(D)J RECOMBINASE
    Michael 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. ..
  5. MECHANISM AND REGULATION OF NONHOMOLOGOUS DNA ENDJOINING
    Michael 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. ..
  6. MECHANISMS OF HUMAN LYMPHOID CHROMOSOMAL TRANSLOCATION
    Michael 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. ..
  7. MECHANISM OF DNA RECOMBINATION AT CLASS SWITCH SEQUENCES
    Michael 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. ..
  8. NORMAL AND MUTANT LYMPHOID V(D)J RECOMBINASE
    Michael 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. ..
  9. MECHANISM OF DNA RECOMBINATION AT CLASS SWITCH SEQUENCES
    Michael 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. ..
  10. NORMAL AND MUTANT LYMPHOID V(D)J RECOMBINASE
    Michael 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. ..
  11. NORMAL AND MUTANT LYMPHOID V(D)J RECOMBINASE
    Michael 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. ..
  12. HUMAN V(D)J RECOMBINASE IN NEOPLASTIC AND PRIMARY CELLS
    Michael Lieber; Fiscal Year: 1999
    ....
  13. NORMAL AND MUTANT LYMPHOID VDJ RECOMBINASE
    Michael 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. ..
  14. MECHANISM OF DNA RECOMBINATION AT CLASS SWITCH SEQUENCES
    Michael Lieber; Fiscal Year: 2001
    ..Fifth, we search for enzymatic activities in extracts that carry out the cleavage step in class switch recombination. ..