DNA strand break repair and human genetic disease.

Each day tens of thousands of DNA single-strand breaks (SSBs) arise in every cell from the attack of deoxyribose and DNA bases by reactive oxygen species and other electrophilic molecules. DNA double-strand breaks (DSBs) also arise, albeit at a much lower frequency, from similar attacks and from the encounter of unrepaired SSBs and possibly other DNA structures by DNA replication forks. DSBs are also created during normal development of the immune system. Defects in the cellular response to DNA strand breaks underpin many human diseases, including disorders associated with cancer predisposition, immune dysfunction, radiosensitivity, and neurodegeneration. Here we provide an overview of the genetic diseases associated with defects in the repair/response to DNA strand breaks.

[1]  Chunyan Liu,et al.  Repair of topoisomerase I covalent complexes in the absence of the tyrosyl-DNA phosphodiesterase Tdp1 , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[2]  S. Powell,et al.  Nonhomologous end-joining of ionizing radiation-induced DNA double-stranded breaks in human tumor cells deficient in BRCA1 or BRCA2. , 2001, Cancer research.

[3]  S. Lees-Miller,et al.  Repair of DNA double strand breaks by non-homologous end joining. , 2003, Biochimie.

[4]  F. Alt,et al.  Increased ionizing radiation sensitivity and genomic instability in the absence of histone H2AX , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Karl-Heinz Krause,et al.  Aberrant expression of BARD1 in breast and ovarian cancers with poor prognosis , 2006, International journal of cancer.

[6]  M. West,et al.  XRCC1 keeps DNA from getting stranded. , 2000, Mutation research.

[7]  A. Ashworth,et al.  Mutation in Brca2 stimulates error‐prone homology‐directed repair of DNA double‐strand breaks occurring between repeated sequences , 2001, The EMBO journal.

[8]  Hans Joenje,et al.  Biallelic Inactivation of BRCA2 in Fanconi Anemia , 2002, Science.

[9]  A. Shinohara,et al.  The controlling role of ATM in homologous recombinational repair of DNA damage , 2000, The EMBO journal.

[10]  J. Lamerdin,et al.  Fanconi Anemia FANCG Protein in Mitigating Radiation- and Enzyme-Induced DNA Double-Strand Breaks by Homologous Recombination in Vertebrate Cells , 2003, Molecular and Cellular Biology.

[11]  C. Wang,et al.  Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response. , 1999, Science.

[12]  M. James,et al.  Relation between the human fibroblast strain 46BR and cell lines representative of Bloom's syndrome. , 1988, Cancer research.

[13]  D. Haber.  BRCA1: an emerging role in the cellular response to DNA damage , 2000, The Lancet.

[14]  Wei Zhou,et al.  T7 RNA polymerase bypass of large gaps on the template strand reveals a critical role of the nontemplate strand in elongation , 1995, Cell.

[15]  P. Doetsch,et al.  Transcription bypass or blockage at single-strand breaks on the DNA template strand: effect of different 3' and 5' flanking groups on the T7 RNA polymerase elongation complex. , 1994, Biochemistry.

[16]  Gemma K. Alderton,et al.  Regulation of mitotic entry by microcephalin and its overlap with ATR signalling , 2006, Nature Cell Biology.

[17]  A. Venkitaraman,et al.  Stabilization of stalled DNA replication forks by the BRCA2 breast cancer susceptibility protein. , 2003, Genes & development.

[18]  C. Campbell,et al.  A Rad50-dependent pathway of DNA repair is deficient in Fanconi anemia fibroblasts. , 2004, Nucleic acids research.

[19]  Gilbert Chu,et al.  Processing of DNA for nonhomologous end‐joining by cell‐free extract , 2005, The EMBO journal.

[20]  A. D’Andrea,et al.  ATR couples FANCD2 monoubiquitination to the DNA-damage response. , 2004, Genes & development.

[21]  Xingzhi Xu,et al.  Microcephalin Is a DNA Damage Response Protein Involved in Regulation of CHK1 and BRCA1*♦ , 2004, Journal of Biological Chemistry.

[22]  D. Sgroi,et al.  BACH1, a Novel Helicase-like Protein, Interacts Directly with BRCA1 and Contributes to Its DNA Repair Function , 2001, Cell.

[23]  David Lombard,et al.  Defective DNA Repair and Increased Genomic Instability in Artemis-deficient Murine Cells , 2003, The Journal of experimental medicine.

[24]  J. Petrini,et al.  The cellular response to DNA double-strand breaks: defining the sensors and mediators. , 2003, Trends in cell biology.

[25]  Peter J McKinnon,et al.  Linking DNA damage and neurodegeneration , 2000, Trends in Neurosciences.

[26]  Alexander Kinev,et al.  BRCA1 Is Associated with a Human SWI/SNF-Related Complex Linking Chromatin Remodeling to Breast Cancer , 2000, Cell.

[27]  S. Jackson,et al.  XLF Interacts with the XRCC4-DNA Ligase IV Complex to Promote DNA Nonhomologous End-Joining , 2006, Cell.

[28]  M. Weinfeld,et al.  Involvement of polynucleotide kinase in a poly(ADP-ribose) polymerase-1-dependent DNA double-strand breaks rejoining pathway. , 2006, Journal of molecular biology.

[29]  B. Koller,et al.  BRCA1 deficient embryonic stem cells display a decreased homologous recombination frequency and an increased frequency of non-homologous recombination that is corrected by expression of a Brca1 transgene , 1999, Oncogene.

[30]  D. Durocher,et al.  Xrcc4 physically links DNA end processing by polynucleotide kinase to DNA ligation by DNA ligase IV , 2004, The EMBO journal.

[31]  A. D’Andrea,et al.  Functional Interaction of Monoubiquitinated FANCD2 and BRCA2/FANCD1 in Chromatin , 2004, Molecular and Cellular Biology.

[32]  P. Jeggo,et al.  DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. , 2001, Molecular cell.

[33]  T. Ohta,et al.  The RING Heterodimer BRCA1-BARD1 Is a Ubiquitin Ligase Inactivated by a Breast Cancer-derived Mutation* , 2001, The Journal of Biological Chemistry.

[34]  C. Lilley,et al.  The Mre11 complex is required for ATM activation and the G2/M checkpoint , 2003, The EMBO journal.

[35]  R. Moses,et al.  BRCA1 interacts directly with the Fanconi anemia protein FANCA. , 2002, Human molecular genetics.

[36]  J. Petrini,et al.  The Rad50 hook domain is a critical determinant of Mre11 complex functions , 2005, Nature Structural &Molecular Biology.

[37]  G. Poirier,et al.  Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. , 1999, The Biochemical journal.

[38]  R. Eeles,et al.  Mutations in BRCA1 and BRCA2 and predisposition to prostate cancer , 2003, The Lancet.

[39]  T. Lindahl,et al.  Defective neurogenesis resulting from DNA ligase IV deficiency requires Atm. , 2000, Genes & development.

[40]  Jiri Bartek,et al.  Cell-cycle checkpoints and cancer , 2004, Nature.

[41]  P. Byrd,et al.  Ataxia-telangiectasia-like disorder (ATLD)-its clinical presentation and molecular basis. , 2004, DNA repair.

[42]  Phang-lang Chen,et al.  Deficient nonhomologous end-joining activity in cell-free extracts from Brca1-null fibroblasts. , 2002, Cancer research.

[43]  R. Gatti,et al.  Ataxia-telangiectasia, an evolving phenotype. , 2004, DNA repair.

[44]  S. Elledge,et al.  Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress. , 2000, Genes & development.

[45]  William F. Morgan,et al.  A Murine Model of Nijmegen Breakage Syndrome , 2002, Current Biology.

[46]  J. Lupski,et al.  Mutation of TDP1, encoding a topoisomerase I–dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy , 2002, Nature Genetics.

[47]  Sara G. Becker-Catania,et al.  The pathogenesis of ataxia-telangiectasia , 2001, Clinical reviews in allergy & immunology.

[48]  Christopher G Mathew,et al.  Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways. , 2004, Human molecular genetics.

[49]  A. Ashworth,et al.  Interaction between the Product of the Breast Cancer Susceptibility Gene BRCA2 and DSS1, a Protein Functionally Conserved from Yeast to Mammals , 1999, Molecular and Cellular Biology.

[50]  A. Fischer,et al.  Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis. , 2003, The Journal of clinical investigation.

[51]  J. Lupski,et al.  Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1 , 2005, Nature.

[52]  B. Trask,et al.  Mutations in the BRCA1-associated RING domain (BARD1) gene in primary breast, ovarian and uterine cancers. , 1998, Human molecular genetics.

[53]  P. Jeggo,et al.  Analysis of DNA ligase IV mutations found in LIG4 syndrome patients: the impact of two linked polymorphisms. , 2004, Human molecular genetics.

[54]  D. Bentley,et al.  Identification of the breast cancer susceptibility gene BRCA2 , 1995, Nature.

[55]  Weidong Wang,et al.  Fanconi Anemia Proteins Are Required To Prevent Accumulation of Replication-Associated DNA Double-Strand Breaks , 2006, Molecular and Cellular Biology.

[56]  T. Mak,et al.  Brca1 required for T cell lineage development but not TCR loci rearrangement , 2000, Nature Immunology.

[57]  D. Ramsden,et al.  Ku protein stimulates DNA end joining by mammalian DNA ligases: a direct role for Ku in repair of DNA double‐strand breaks , 1998, The EMBO journal.

[58]  K. Caldecott.  DNA Single-Strand Break Repair and Spinocerebellar Ataxia , 2003, Cell.

[59]  A. Ashworth,et al.  DSS1 is required for RAD51 focus formation and genomic stability in mammalian cells , 2004, EMBO reports.

[60]  Luke Hughes-Davies,et al.  EMSY Links the BRCA2 Pathway to Sporadic Breast and Ovarian Cancer , 2003, Cell.

[61]  Y. Shiloh.  ATM and related protein kinases: safeguarding genome integrity , 2003, Nature Reviews Cancer.

[62]  Zhiyuan Shen,et al.  The BRCA2-Interacting Protein BCCIP Functions in RAD51 and BRCA2 Focus Formation and Homologous Recombinational Repair , 2005, Molecular and Cellular Biology.

[63]  S. West,et al.  The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates , 2006, Nature.

[64]  H. Kitao,et al.  A FancD2-monoubiquitin fusion reveals hidden functions of Fanconi anemia core complex in DNA repair. , 2005, Molecular cell.

[65]  Stephen C. West,et al.  Molecular views of recombination proteins and their control , 2003, Nature Reviews Molecular Cell Biology.

[66]  J. Pouliot,et al.  Pathways for repair of topoisomerase I covalent complexes in Saccharomyces cerevisiae , 2001, Genes to cells : devoted to molecular & cellular mechanisms.

[67]  John R Yates,et al.  The hMre11/hRad50 Protein Complex and Nijmegen Breakage Syndrome: Linkage of Double-Strand Break Repair to the Cellular DNA Damage Response , 1998, Cell.

[68]  D. Papadopoulo,et al.  Fidelity of DNA double-strand break repair in heterozygous cell lines harbouring BRCA1 missense mutations , 2004, Oncogene.

[69]  A. D’Andrea,et al.  The Fanconi anemia pathway is required for the DNA replication stress response and for the regulation of common fragile site stability. , 2005, Human molecular genetics.

[70]  K. Manova,et al.  Role of Nbs1 in the activation of the Atm kinase revealed in humanized mouse models , 2005, Nature Cell Biology.

[71]  M. Kastan,et al.  DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation , 2003, Nature.

[72]  H. Arakawa,et al.  Fanconi Anemia Protein FANCD2 Promotes Immunoglobulin Gene Conversion and DNA Repair through a Mechanism Related to Homologous Recombination , 2005, Molecular and Cellular Biology.

[73]  A. Ashworth,et al.  Direct interaction of the Fanconi anaemia protein FANCG with BRCA2/FANCD1. , 2003, Human molecular genetics.

[74]  A. Kuzminov.  Single-strand interruptions in replicating chromosomes cause double-strand breaks , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[75]  D. Ramsden,et al.  Ku heterodimer binds to both ends of the Werner protein and functional interaction occurs at the Werner N-terminus. , 2002, Nucleic acids research.

[76]  C. Deng,et al.  BRCA1 Supports XIST RNA Concentration on the Inactive X Chromosome , 2002, Cell.

[77]  S. Jackson,et al.  Evolutionary and Functional Conservation of the DNA Non-homologous End-joining Protein, XLF/Cernunnos* , 2006, Journal of Biological Chemistry.

[78]  A. Fischer,et al.  Cernunnos, a Novel Nonhomologous End-Joining Factor, Is Mutated in Human Immunodeficiency with Microcephaly , 2006, Cell.

[79]  T. Stankovic,et al.  The DNA Double-Strand Break Repair Gene hMRE11 Is Mutated in Individuals with an Ataxia-Telangiectasia-like Disorder , 1999, Cell.

[80]  D. Papadopoulo,et al.  A single mutated BRCA1 allele leads to impaired fidelity of double strand break end-joining , 2002, Oncogene.

[81]  J. Manley,et al.  Functional interaction of BRCA1-associated BARD1 with polyadenylation factor CstF-50. , 1999, Science.

[82]  N. Pavletich,et al.  The BRCA2-interacting protein DSS1 is vital for DNA repair, recombination, and genome stability in Ustilago maydis. , 2003, Molecular cell.

[83]  Charles Brenner,et al.  Hint, Fhit, and GalT: function, structure, evolution, and mechanism of three branches of the histidine triad superfamily of nucleotide hydrolases and transferases. , 2002, Biochemistry.

[84]  J. Ott,et al.  The BRCA1-interacting helicase BRIP1 is deficient in Fanconi anemia , 2005, Nature Genetics.

[85]  C. Dekker,et al.  Mesoscale conformational changes in the DNA-repair complex Rad50/Mre11/Nbs1 upon binding DNA , 2005, Nature.

[86]  Susan M. Gordon,et al.  Tetratricopeptide-motif-mediated interaction of FANCG with recombination proteins XRCC3 and BRCA2. , 2006, DNA repair.

[87]  N. Pavletich,et al.  The BRCA2 homologue Brh2 nucleates RAD51 filament formation at a dsDNA–ssDNA junction , 2005, Nature.

[88]  C. Mathew,et al.  Interaction of FANCD2 and NBS1 in the DNA damage response , 2002, Nature Cell Biology.

[89]  J. Bartek,et al.  Distinct spatiotemporal dynamics of mammalian checkpoint regulators induced by DNA damage , 2003, Nature Cell Biology.

[90]  C. Deng.  BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution , 2006, Nucleic acids research.

[91]  B. Chen,et al.  A New XRCC1-Containing Complex and Its Role in Cellular Survival of Methyl Methanesulfonate Treatment , 2004, Molecular and Cellular Biology.

[92]  T. Blundell,et al.  Dynamic control of Rad51 recombinase by self-association and interaction with BRCA2. , 2003, Molecular cell.

[93]  S. Sugano,et al.  Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene , 2001, Nature Genetics.

[94]  R. Shiekhattar,et al.  Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair. , 2003, Molecular cell.

[95]  F. Couch,et al.  BRCA1 Facilitates Stress-induced Apoptosis in Breast and Ovarian Cancer Cell Lines* , 2000, The Journal of Biological Chemistry.

[96]  V. Yamazaki,et al.  A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage , 2000, Current Biology.

[97]  S. Elledge,et al.  Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks. , 1999, Science.

[98]  Michael M. Murphy,et al.  ATM Phosphorylates Histone H2AX in Response to DNA Double-strand Breaks* , 2001, The Journal of Biological Chemistry.

[99]  S. Tsuji,et al.  Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein , 2004, Annals of neurology.

[100]  Thomas Ludwig,et al.  The BRCA1/BARD1 heterodimer, a tumor suppressor complex with ubiquitin E3 ligase activity. , 2002, Current opinion in genetics & development.

[101]  R. T. Bree,et al.  The MRN complex: coordinating and mediating the response to broken chromosomes , 2003, EMBO reports.

[102]  P. Oefner,et al.  Contributions of ATM mutations to familial breast and ovarian cancer. , 2003, Cancer research.

[103]  S C West,et al.  Role of BRCA2 in control of the RAD51 recombination and DNA repair protein. , 2001, Molecular cell.

[104]  M. W. Thompson,et al.  Specific cellular defects in patients with Fanconi anemia , 1979, Journal of cellular physiology.

[105]  F. Alt,et al.  Checkpoint failure and chromosomal instability without lymphomagenesis in Mre11(ATLD1/ATLD1) mice. , 2003, Molecular cell.

[106]  A. Nussenzweig,et al.  DNA damage-induced G2–M checkpoint activation by histone H2AX and 53BP1 , 2002, Nature Cell Biology.

[107]  G E Tomlinson,et al.  BRCA2 is required for ionizing radiation-induced assembly of Rad51 complex in vivo. , 1999, Cancer research.

[108]  M. Story,et al.  Artemis Is a Phosphorylation Target of ATM and ATR and Is Involved in the G2/M DNA Damage Checkpoint Response , 2004, Molecular and Cellular Biology.

[109]  S. Jackson,et al.  The MRE11 complex: at the crossroads of DNA repair and checkpoint signalling , 2002, Nature Reviews Molecular Cell Biology.

[110]  P. Doetsch,et al.  Effects of abasic sites and DNA single-strand breaks on prokaryotic RNA polymerases. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[111]  R. Bonner,et al.  Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks , 2003, Nature Cell Biology.

[112]  Tom L. Blundell,et al.  Insights into DNA recombination from the structure of a RAD51–BRCA2 complex , 2002, Nature.

[113]  G. Iliakis,et al.  Deficiency of human BRCA2 leads to impaired homologous recombination but maintains normal nonhomologous end joining , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[114]  M. Jasin,et al.  BRCA2 is required for homology-directed repair of chromosomal breaks. , 2001, Molecular cell.

[115]  S. West,et al.  Involvement of human polynucleotide kinase in double‐strand break repair by non‐homologous end joining , 2002, The EMBO journal.

[116]  K. Caldecott.  XRCC1 and DNA strand break repair. , 2003, DNA repair.

[117]  J. Ward,et al.  Mouse Models of Human Familial Cancer Syndromes , 2004, Toxicologic pathology.

[118]  L. Starita,et al.  The multiple nuclear functions of BRCA1: transcription, ubiquitination and DNA repair. , 2003, Current opinion in cell biology.

[119]  T. E. Wilson,et al.  Yeast Tdp1 and Rad1-Rad10 function as redundant pathways for repairing Top1 replicative damage , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[120]  Wen-Hwa Lee,et al.  BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure. , 2002, Science.

[121]  A. D’Andrea,et al.  S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51. , 2002, Blood.

[122]  Yair Andegeko,et al.  Requirement of the MRN complex for ATM activation by DNA damage , 2003, The EMBO journal.

[123]  D. Livingston,et al.  BRCA1, BRCA2, and Rad51 operate in a common DNA damage response pathway. , 1999, Cancer research.

[124]  P. Jeggo,et al.  DNA‐PK autophosphorylation facilitates Artemis endonuclease activity , 2006, The EMBO journal.

[125]  Zhao-Qi Wang,et al.  Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[126]  Phang-lang Chen,et al.  BRCA1 Facilitates Microhomology-mediated End Joining of DNA Double Strand Breaks* , 2002, The Journal of Biological Chemistry.

[127]  S. Jackson,et al.  Interfaces Between the Detection, Signaling, and Repair of DNA Damage , 2002, Science.

[128]  Steven E. Bayer,et al.  A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. , 1994, Science.

[129]  S. Cantor,et al.  BACH1 is critical for homologous recombination and appears to be the Fanconi anemia gene product FANCJ. , 2005, Cancer cell.

[130]  Yunmei Ma,et al.  Hairpin Opening and Overhang Processing by an Artemis/DNA-Dependent Protein Kinase Complex in Nonhomologous End Joining and V(D)J Recombination , 2002, Cell.

[131]  Minoru Takata,et al.  Functional Interplay between BRCA2/FancD1 and FancC in DNA Repair* , 2006, Journal of Biological Chemistry.

[132]  P. Jeggo,et al.  The life and death of DNA-PK , 2005, Oncogene.

[133]  I. Demuth,et al.  Attenuation of the formation of DNA-repair foci containing RAD51 in Fanconi anaemia. , 2002, Carcinogenesis.

[134]  F. Couch,et al.  Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. , 1998, Molecular cell.

[135]  D. Averbeck,et al.  DNA cross-link-dependent RAD50/MRE11/NBS1 subnuclear assembly requires the Fanconi anemia C protein. , 2002, Human molecular genetics.

[136]  C. Deng,et al.  Multiple Endonucleases Function to Repair Covalent Topoisomerase I Complexes in Saccharomyces cerevisiae , 2005, Genetics.

[137]  J. Glover,et al.  Structural basis for phosphorylation-dependent signaling in the DNA-damage response. , 2005, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[138]  C. Brenner,et al.  The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4. , 2004, DNA repair.

[139]  Ji-Hoon Lee,et al.  Direct Activation of the ATM Protein Kinase by the Mre11/Rad50/Nbs1 Complex , 2004, Science.

[140]  M. James,et al.  A biochemical defect in the repair of alkylated DNA in cells from an immunodeficient patient (46BR). , 1983, Carcinogenesis.

[141]  C. Campbell,et al.  A DNA Double Strand Break Repair Defect in Fanconi Anemia Fibroblasts* , 2002, The Journal of Biological Chemistry.

[142]  Yves Pommier,et al.  Association of XRCC1 and tyrosyl DNA phosphodiesterase (Tdp1) for the repair of topoisomerase I-mediated DNA lesions. , 2003, DNA repair.

[143]  D. Ramsden,et al.  Ku Recruits the XRCC4-Ligase IV Complex to DNA Ends , 2000, Molecular and Cellular Biology.

[144]  K. Naka,et al.  DNA damage tumor suppressor genes and genomic instability. , 2004, Current opinion in genetics & development.

[145]  N. Shao,et al.  Induction of apoptosis by the tumor suppressor protein BRCA1. , 1996, Oncogene.

[146]  A. Monteiro,et al.  BRCA1: exploring the links to transcription. , 2000, Trends in biochemical sciences.

[147]  A. Fischer,et al.  Artemis, a Novel DNA Double-Strand Break Repair/V(D)J Recombination Protein, Is Mutated in Human Severe Combined Immune Deficiency , 2001, Cell.

[148]  D. Barnes,et al.  Specific Function of DNA Ligase I in Simian Virus 40 DNA Replication by Human Cell-free Extracts Is Mediated by the Amino-terminal Non-catalytic Domain* , 1997, The Journal of Biological Chemistry.

[149]  D. Livingston,et al.  The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[150]  J. Hoeijmakers,et al.  Fanconi Anemia (Cross)linked to DNA Repair , 2005, Cell.

[151]  Stephen J. Elledge,et al.  MDC1 is a mediator of the mammalian DNA damage checkpoint , 2003, Nature.

[152]  M. Kastan,et al.  Involvement of the cohesin protein, Smc1, in Atm-dependent and independent responses to DNA damage. , 2002, Genes & development.

[153]  S. Ganesan,et al.  Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway. , 2001, Molecular cell.

[154]  O. Delattre,et al.  Absence of major defects in non-homologous DNA end joining in human breast cancer cell lines , 2002, Oncogene.

[155]  P. Mckinnon.  ATM and ataxia telangiectasia , 2004, EMBO reports.

[156]  T. Gibson,et al.  The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin , 2001, Nature Genetics.

[157]  Z. Herceg,et al.  The Fanconi anemia group A protein modulates homologous repair of DNA double-strand breaks in mammalian cells. , 2005, Carcinogenesis.

[158]  A. Nussenzweig,et al.  Autophosphorylation at serine 1987 is dispensable for murine Atm activation in vivo , 2006, Nature.

[159]  P. Jeggo,et al.  A subset of ATM‐ and ATR‐dependent phosphorylation events requires the BRCA1 protein , 2003, The EMBO journal.

[160]  Martin Kühne,et al.  A pathway of double-strand break rejoining dependent upon ATM, Artemis, and proteins locating to gamma-H2AX foci. , 2004, Molecular cell.

[161]  J. Kobayashi,et al.  Molecular mechanism of the recruitment of NBS1/hMRE11/hRAD50 complex to DNA double-strand breaks: NBS1 binds to gamma-H2AX through FHA/BRCT domain. , 2004, Journal of radiation research.

[162]  P. Jeggo,et al.  An overview of three new disorders associated with genetic instability: LIG4 syndrome, RS-SCID and ATR-Seckel syndrome. , 2004, DNA repair.

[163]  S. West,et al.  CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair , 2005, Nature.

[164]  B. Koller,et al.  Brca1 controls homology-directed DNA repair. , 1999, Molecular cell.

[165]  E. Rosen,et al.  BRCA1 Inhibition of Telomerase Activity in Cultured Cells , 2003, Molecular and Cellular Biology.

[166]  Ji-Hoon Lee,et al.  ATM Activation by DNA Double-Strand Breaks Through the Mre11-Rad50-Nbs1 Complex , 2005, Science.

[167]  M. Kastan,et al.  Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway. , 2004, Genes & development.

[168]  A. Barzilai,et al.  ATM deficiency and oxidative stress: a new dimension of defective response to DNA damage. , 2002, DNA repair.

[169]  S. Nocentini,et al.  Comet assay analysis of repair of DNA strand breaks in normal and deficient human cells exposed to radiations and chemicals. Evidence for a repair pathway specificity of DNA ligation. , 1995, Radiation research.

[170]  J. Tainer,et al.  The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair , 2002, Nature.

[171]  F. Alt,et al.  Genetic interactions between ATM and the nonhomologous end-joining factors in genomic stability and development , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[172]  F. Gumy-Pause,et al.  ATM gene and lymphoid malignancies , 2004, Leukemia.

[173]  R. Weichselbaum,et al.  The Breast Cancer Susceptibility Gene BRCA1 Is Required for Subnuclear Assembly of Rad51 and Survival following Treatment with the DNA Cross-linking Agent Cisplatin* , 2000, The Journal of Biological Chemistry.

[174]  D. Melton,et al.  Phenotypic correction of a human cell line (46BR) with aberrant DNA ligase I activity. , 1993, Mutation research.

[175]  S. Elledge,et al.  BRIT1/MCPH1 is a DNA damage responsive protein that regulates the Brca1-Chk1 pathway, implicating checkpoint dysfunction in microcephaly. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[176]  R. Moses,et al.  Reactivation of psoralen-reacted plasmid DNA in Fanconi anemia, xeroderma pigmentosum, and normal human fibroblast cells , 1991, Somatic cell and molecular genetics.

[177]  E. Rogakou,et al.  DNA Double-stranded Breaks Induce Histone H2AX Phosphorylation on Serine 139* , 1998, The Journal of Biological Chemistry.

[178]  Sheila Seal,et al.  BRCA2 mutations in primary breast and ovarian cancers , 1996, Nature Genetics.

[179]  Yanfen Hu,et al.  Chromatin remodeling and activation of chromosomal DNA replication by an acidic transcriptional activation domain from BRCA1. , 1999, Genes & development.

[180]  D. Barnes,et al.  Mutations in the DNA ligase I gene of an individual with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents , 1992, Cell.

[181]  Yunmei Ma,et al.  A biochemically defined system for mammalian nonhomologous DNA end joining. , 2004, Molecular cell.

[182]  K. Cerosaletti,et al.  A patient with mutations in DNA Ligase IV: Clinical features and overlap with Nijmegen breakage syndrome , 2005, American journal of medical genetics. Part A.

[183]  David J. Chen,et al.  Artemis deficiency confers a DNA double-strand break repair defect and Artemis phosphorylation status is altered by DNA damage and cell cycle progression. , 2005, DNA repair.

[184]  M. Lavin,et al.  Involvement of novel autophosphorylation sites in ATM activation , 2006, The EMBO journal.

[185]  Xiaofeng Jiang,et al.  A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[186]  A. Olshen,et al.  BARD1 Participates with BRCA1 in Homology-Directed Repair of Chromosome Breaks , 2003, Molecular and Cellular Biology.

[187]  Anne M. Bowcock,et al.  Identification of a RING protein that can interact in vivo with the BRCA1 gene product , 1996, Nature Genetics.

[188]  Yunmei Ma,et al.  Mechanism and regulation of human non-homologous DNA end-joining , 2003, Nature Reviews Molecular Cell Biology.

[189]  Jong-Soo Lee,et al.  hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response , 2000, Nature.

[190]  S. Aaronson,et al.  BRCA2 Is Ubiquitinated In Vivo and Interacts with USP11, a Deubiquitinating Enzyme That Exhibits Prosurvival Function in the Cellular Response to DNA Damage , 2004, Molecular and Cellular Biology.

[191]  D. Stoppa-Lyonnet,et al.  Phenotypic cellular characterization of an Ataxia telangiectasia patient carrying a causal homozygous missense mutation , 2003, Human mutation.