Radiation and the cell cycle, revisited

The cell cycle has been inextricably linked to the cellular response to radiation for many years. However, it is only in the past decade that the concept of a coordinated DNA damage response integrating damage recognition, cell cycle checkpoints and DNA repair has begun to be elucidated. The ATM protein is emerging as a key orchestrator of the damage response activating a wide variety of effectors involved in cell cycle arrest and DNA repair to elicit a concerted effort to prevent genome instability caused by unwanted changes in DNA sequence. The key proteins involved in cell cycle checkpoints in different phases of the cell cycle, and their interaction, is a fertile and rapidly developing area of research. This review summarizes the current state of knowledge of cellular checkpoints in response to radiation-induced double-strand breaks in mammalian cells and how this impacts on radiosensitivity.

[1]  Wafik S El-Deiry,et al.  P53 and radiation responses , 2003, Oncogene.

[2]  J. Bartek,et al.  Mammalian G1- and S-phase checkpoints in response to DNA damage. , 2001, Current opinion in cell biology.

[3]  A. Howard,et al.  Nuclear incorporation of P32 as demonstrated by autoradiographs , 1951 .

[4]  J. Petrini,et al.  DNA Damage-Dependent Nuclear Dynamics of the Mre11 Complex , 2001, Molecular and Cellular Biology.

[5]  Jun Qin,et al.  ATR and ATRIP: Partners in Checkpoint Signaling , 2001, Science.

[6]  K. Khanna,et al.  Chk2 Activation Dependence on Nbs1 after DNA Damage , 2001, Molecular and Cellular Biology.

[7]  C. M. Rusk,et al.  A cell kinetic method for the mitotic selection of treated G2 cells. , 1983, Cell and tissue kinetics.

[8]  David J. Chen,et al.  DNA-dependent protein kinase suppresses double-strand break-induced and spontaneous homologous recombination , 2002, Proceedings of the National Academy of Sciences of the United States of America.

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

[10]  H. Piwnica-Worms,et al.  The G2 DNA Damage Checkpoint Delays Expression of Genes Encoding Mitotic Regulators* , 2001, The Journal of Biological Chemistry.

[11]  Jiri Bartek,et al.  Chk1 and Chk2 kinases in checkpoint control and cancer. , 2003, Cancer cell.

[12]  Y. Xiong,et al.  A p53 Amino-Terminal Nuclear Export Signal Inhibited by DNA Damage-Induced Phosphorylation , 2001, Science.

[13]  D. Donoghue,et al.  cdc25+ encodes a protein phosphatase that dephosphorylates p34cdc2. , 1992, Molecular biology of the cell.

[14]  Bo Xu,et al.  Involvement of Brca1 in S-Phase and G2-Phase Checkpoints after Ionizing Irradiation , 2001, Molecular and Cellular Biology.

[15]  S. Jackson,et al.  The complex matter of DNA double-strand break detection. , 2001, Biochemical Society transactions.

[16]  D. Baltimore,et al.  Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance. , 2003, Genes & development.

[17]  P. Kaldis.  The cdk-activating kinase (CAK): from yeast to mammals , 1999, Cellular and Molecular Life Sciences CMLS.

[18]  H. Piwnica-Worms,et al.  p107wee1 is a dual-specificity kinase that phosphorylates p34cdc2 on tyrosine 15. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[19]  J. Murnane,et al.  Cell checkpoint and radiosensitivity , 1993, Nature.

[20]  D. Hill,et al.  Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin. , 1998, Cancer Research.

[21]  P. Jeggo,et al.  Radiosensitivity in Nijmegen Breakage Syndrome cells is attributable to a repair defect and not cell cycle checkpoint defects. , 2000, Cancer research.

[22]  Bo Xu,et al.  ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway , 2000, Nature.

[23]  J. Bartek,et al.  Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent Phosphorylation of Chk1 on Ser-317 in Response to Ionizing Radiation* , 2003, The Journal of Biological Chemistry.

[24]  D. Stokoe,et al.  A Role for PI 3-Kinase and PKB Activity in the G2/M Phase of the Cell Cycle , 2002, Current Biology.

[25]  Y. Shiloh,et al.  Relationship of the ataxia-telangiectasia protein ATM to phosphoinositide 3-kinase. , 1995, TIBS -Trends in Biochemical Sciences. Regular ed.

[26]  L. Tolmach,et al.  X-Ray Sensitivity and DNA Synthesis in Synchronous Populations of HeLa Cells , 1963, Science.

[27]  G. Stark,et al.  Regulation of the G2/M transition by p53 , 2001, Oncogene.

[28]  H. Taubert,et al.  Loss of G2/M arrest correlates with radiosensitization in two human sarcoma cell lines with mutant p53 , 2001, International journal of cancer.

[29]  H. Sussman,et al.  Restoration of the G1 checkpoint and the apoptotic pathway mediated by wild-type p53 sensitizes squamous cell carcinoma of the head and neck to radiotherapy. , 1997, Archives of otolaryngology--head & neck surgery.

[30]  S. J. Park,et al.  The radiation hypersensitivity of cells at mitosis , 2002, International journal of radiation biology.

[31]  S. Roberts,et al.  Radiation-induced G2 Delay and Spontaneous Chromosome Aberrations in Ataxia-telangiectasia Homozygotes and Heterozygotes. , 1994, International Journal of Radiation Biology.

[32]  C. Peng,et al.  Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. , 1997, Science.

[33]  L. Tolmach,et al.  Changes in X-ray Sensitivity of HeLa Cells during the Division Cycle , 1961, Nature.

[34]  A. Kumagai,et al.  Positive regulation of Wee1 by Chk1 and 14-3-3 proteins. , 2001, Molecular biology of the cell.

[35]  L. Hartwell,et al.  Genetic control of the cell-division cycle in yeast. I. Detection of mutants. , 1970, Proceedings of the National Academy of Sciences of the United States of America.

[36]  P. Hainaut,et al.  p53 and cell-cycle control: a finger in every pie. , 2000, Pathologie-biologie.

[37]  M. Kastan,et al.  The many substrates and functions of ATM , 2000, Nature Reviews Molecular Cell Biology.

[38]  Michael B. Yaffe,et al.  The Molecular Basis for Phosphodependent Substrate Targeting and Regulation of Plks by the Polo-Box Domain , 2003, Cell.

[39]  D. Brachman,et al.  p53 mutation does not correlate with radiosensitivity in 24 head and neck cancer cell lines. , 1993, Cancer research.

[40]  James K. Chen,et al.  The checkpoint protein Chfr is a ligase that ubiquitinates Plk1 and inhibits Cdc2 at the G2 to M transition , 2002, The Journal of cell biology.

[41]  Francis Collins,et al.  Atm-Deficient Mice: A Paradigm of Ataxia Telangiectasia , 1996, Cell.

[42]  H. Piwnica-Worms,et al.  Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase. , 1992, Science.

[43]  E. Nishida,et al.  Nuclear export of cyclin B1 and its possible role in the DNA damage‐induced G2 checkpoint , 1998, The EMBO journal.

[44]  George Iliakis,et al.  Biochemical evidence for Ku-independent backup pathways of NHEJ. , 2003, Nucleic acids research.

[45]  Q. Zhan,et al.  The mismatch repair system is required for S-phase checkpoint activation , 2003, Nature Genetics.

[46]  A. Carr,et al.  Fission yeast rad17: a homologue of budding yeast RAD24 that shares regions of sequence similarity with DNA polymerase accessory proteins. , 1995, The EMBO journal.

[47]  W. Dewey,et al.  Radiation-induced division delay in synchronized Chinese hamster ovary cells in monolayer culture. , 1972, Radiation research.

[48]  L. Hartwell,et al.  Checkpoints: controls that ensure the order of cell cycle events. , 1989, Science.

[49]  M. Kastan,et al.  Control of G1 arrest after DNA damage. , 1993, Environmental health perspectives.

[50]  R. Medema,et al.  Polo-like kinase-1 is a target of the DNA damage checkpoint , 2000, Nature Cell Biology.

[51]  E. Shtivelman.  Promotion of mitosis by activated protein kinase B after DNA damage involves polo-like kinase 1 and checkpoint protein CHFR. , 2003, Molecular Cancer Research.

[52]  J. Błasiak,et al.  Non-homologous DNA end joining. , 2003, Acta biochimica Polonica.

[53]  M. Montenarh,et al.  Regulation of CAK kinase activity by p53 , 1998, Oncogene.

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

[55]  A. N. Meyer,et al.  Requirement for phosphorylation of cyclin B1 for Xenopus oocyte maturation. , 1995, Molecular biology of the cell.

[56]  L. Hartwell,et al.  Test for temporal or spatial restrictions in gene product function during the cell division cycle , 1983, Molecular and cellular biology.

[57]  P. Graves,et al.  Localization of human Cdc25C is regulated both by nuclear export and 14-3-3 protein binding , 2001, Oncogene.

[58]  W. K. Sinclair.  Cyclic x-ray responses in mammalian cells in vitro. , 1968, Radiation research.

[59]  H. Stürzbecher,et al.  Homologous recombination and cell cycle checkpoints: Rad51 in tumour progression and therapy resistance. , 2003, Toxicology.

[60]  R. Yarden,et al.  BRCA1 interacts with components of the histone deacetylase complex. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[61]  J. Harbour,et al.  The Rb/E2F pathway: expanding roles and emerging paradigms. , 2000, Genes & development.

[62]  N. Walworth,et al.  The G2-phase DNA-damage checkpoint. , 2000, Trends in cell biology.

[63]  Shunichi Takeda,et al.  Nbs1 is essential for DNA repair by homologous recombination in higher vertebrate cells , 2002, Nature.

[64]  N. Mailand,et al.  Involvement of Myc Activity in a G1/S-Promoting Mechanism Parallel to the pRb/E2F Pathway , 2000, Molecular and Cellular Biology.

[65]  L. Hartwell,et al.  Control of G2 delay by the RAD9 gene of Saccharomyces cerevisiae , 1989, Journal of Cell Science.

[66]  R. Painter,et al.  Radiosensitivity in ataxia-telangiectasia: a new explanation. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[67]  M. Groudine,et al.  Abrogation of the G2 checkpoint results in differential radiosensitization of G1 checkpoint-deficient and G1 checkpoint-competent cells. , 1995, Cancer research.

[68]  Y. Yamaguchi-Iwai,et al.  Homologous recombination and non‐homologous end‐joining pathways of DNA double‐strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells , 1998, The EMBO journal.

[69]  Prem Seth,et al.  Cleavage of CDK Inhibitor p21Cip1/Waf1 by Caspases Is an Early Event during DNA Damage-induced Apoptosis* , 1998, The Journal of Biological Chemistry.

[70]  Schneiderman Mh,et al.  A cell kinetic method for the mitotic selection of treated G2 cells. , 1983 .

[71]  W. Mckenna,et al.  Detection of repair activity during the DNA damage-induced G2 delay in human cancer cells , 2001, Oncogene.

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

[73]  K. Weber,et al.  p53, Apoptosis and Radiosensitivity – Experimental and Clinical Data , 2002, Oncology Research and Treatment.

[74]  R. Painter,et al.  Repair replication in mammalian cells after x-irradiation. , 1972, Mutation research.

[75]  E. Friedberg,et al.  DNA damage and repair , 2003, Nature.

[76]  M. Jasin,et al.  Sister chromatid gene conversion is a prominent double‐strand break repair pathway in mammalian cells , 2000, The EMBO journal.

[77]  A. Carr,et al.  Protein kinase mutants of human ATR increase sensitivity to UV and ionizing radiation and abrogate cell cycle checkpoint control. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[78]  R. Muschel,et al.  Cyclin expression and G2-phase delay after irradiation. , 1994, Radiation research.

[79]  J. Debus,et al.  Preferential radiosensitization in p53-mutated human tumour cell lines by pentoxifylline-mediated disruption of the G2/M checkpoint control , 2002, International journal of radiation biology.

[80]  S. Roberts,et al.  Radiation-induced G2 delay and spontaneous chromosome aberrations in ataxia-telangiectasia homozygotes and heterozygotes. , 1994, International journal of radiation biology.

[81]  Huichen Wang,et al.  DNA damage checkpoint control in cells exposed to ionizing radiation , 2003, Oncogene.

[82]  B. Wouters,et al.  An Association between the Radiation-Induced Arrest of G2-Phase Cells and Low-Dose Hyper-Radiosensitivity: A Plausible Underlying Mechanism? , 2003, Radiation research.

[83]  N. Mailand,et al.  The ATM–Chk2–Cdc25A checkpoint pathway guards against radioresistant DNA synthesis , 2001, Nature.

[84]  R. Abraham.  Cell cycle checkpoint signaling through the ATM and ATR kinases. , 2001, Genes & development.

[85]  Bo Xu,et al.  Distinct functions of Nijmegen breakage syndrome in ataxia telangiectasia mutated-dependent responses to DNA damage. , 2003, Molecular cancer research : MCR.

[86]  R. Slebos,et al.  Loss of a p53-associated G1 checkpoint does not decrease cell survival following DNA damage. , 1993, Cancer research.

[87]  S. T. Kim,et al.  Substrate Specificities and Identification of Putative Substrates of ATM Kinase Family Members* , 1999, The Journal of Biological Chemistry.

[88]  T. Weinert,et al.  Toward maintaining the genome: DNA damage and replication checkpoints. , 2002, Annual review of genetics.

[89]  R. Muschel,et al.  Effects of ionizing radiation on cyclin expression in HeLa cells. , 1992, Radiation research.

[90]  M. Lavin,et al.  Radiosensitivity in ataxia-telangiectasia: anomalies in radiation-induced cell cycle delay. , 1994, International journal of radiation biology.

[91]  H. Piwnica-Worms,et al.  Overproduction of Human Myt1 Kinase Induces a G2 Cell Cycle Delay by Interfering with the Intracellular Trafficking of Cdc2-Cyclin B1 Complexes , 1999, Molecular and Cellular Biology.

[92]  A. Giaccia,et al.  The complexity of p53 modulation: emerging patterns from divergent signals. , 1998, Genes & development.

[93]  L. Hartwell,et al.  Unequal division in Saccharomyces cerevisiae and its implications for the control of cell division , 1977, The Journal of cell biology.

[94]  S. Jackson,et al.  DNA-dependent protein kinase. , 1997, The international journal of biochemistry & cell biology.

[95]  T. Hunter,et al.  The differential localization of human cyclins A and B is due to a cytoplasmic retention signal in cyclin B. , 1994, The EMBO journal.

[96]  S. Elledge,et al.  DNA damage-induced activation of p53 by the checkpoint kinase Chk2. , 2000, Science.

[97]  D. Lydall,et al.  Yeast Checkpoint Genes in DNA Damage Processing: Implications for Repair and Arrest , 1995, Science.

[98]  Yonghong Xiao,et al.  Association of BRCA1 with Rad51 in Mitotic and Meiotic Cells , 1997, Cell.

[99]  J. D. Chapman,et al.  The intrinsic radiosensitivity of some human tumor cells throughout their cell cycles. , 1997, Radiation research.

[100]  Bo Xu,et al.  Phosphorylation of serine 1387 in Brca1 is specifically required for the Atm-mediated S-phase checkpoint after ionizing irradiation. , 2002, Cancer research.

[101]  Stephen J. Elledge,et al.  Cell Cycle Checkpoints: Preventing an Identity Crisis , 1996, Science.

[102]  A. Fornace,et al.  p38 and Chk1 kinases: different conductors for the G(2)/M checkpoint symphony. , 2002, Current opinion in genetics & development.

[103]  K. Khanna,et al.  Caffeine Abolishes the Mammalian G2/M DNA Damage Checkpoint by Inhibiting Ataxia-Telangiectasia-mutated Kinase Activity* , 2000, The Journal of Biological Chemistry.

[104]  P. Thuriaux,et al.  Genetic control of the cell division cycle in the fission yeast Schizosaccharomyces pombe , 1976, Molecular and General Genetics MGG.

[105]  S. Elledge,et al.  Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. , 1998, Science.

[106]  L. Tolmach,et al.  Variations in several responses of HeLa cells to x-irradiation during the division cycle. , 1963, Biophysical journal.

[107]  L. Hartwell,et al.  Cell cycle control and cancer. , 1994, Science.

[108]  K. Vousden,et al.  Regulation and function of the p53 tumor suppressor protein. , 2001, Current opinion in cell biology.

[109]  L. Hartwell.  NOBEL LECTURE: Yeast and Cancer , 2002, Bioscience reports.

[110]  L. Hartwell,et al.  The role of S. cerevisiae cell division cycle genes in nuclear fusion. , 1982, Genetics.

[111]  J. Walker,et al.  Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair , 2001, Nature.

[112]  S. Elledge,et al.  Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. , 2000, Genes & development.

[113]  J. M. Lee,et al.  p53 mutations increase resistance to ionizing radiation. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[114]  Kai Rothkamm,et al.  A Double-Strand Break Repair Defect in ATM-Deficient Cells Contributes to Radiosensitivity , 2004, Cancer Research.

[115]  Y Taya,et al.  Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. , 1998, Science.

[116]  J. Haber.  Partners and pathwaysrepairing a double-strand break. , 2000, Trends in genetics : TIG.

[117]  Kai Rothkamm,et al.  Pathways of DNA Double-Strand Break Repair during the Mammalian Cell Cycle , 2003, Molecular and Cellular Biology.

[118]  M. Kastan,et al.  Two Molecularly Distinct G2/M Checkpoints Are Induced by Ionizing Irradiation , 2002, Molecular and Cellular Biology.

[119]  N. Mailand,et al.  Rapid destruction of human Cdc25A in response to DNA damage. , 2000, Science.

[120]  J. Hurwitz,et al.  Purification and characterization of human DNA damage checkpoint Rad complexes , 2001, Proceedings of the National Academy of Sciences of the United States of America.

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

[122]  Y. Shiloh.  Ataxia-Telangiectasia: Closer to Unraveling the Mystery , 1995, European journal of human genetics : EJHG.

[123]  R. Medema,et al.  Inhibition of Polo-like Kinase-1 by DNA Damage Occurs in an ATM- or ATR-dependent Fashion* , 2001, The Journal of Biological Chemistry.

[124]  J. Nickoloff,et al.  Interactive competition between homologous recombination and non-homologous end joining. , 2003, Molecular cancer research : MCR.

[125]  Lawrence C. Brody,et al.  BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage , 2002, Nature Genetics.

[126]  R. Abraham.  Checkpoint signaling: epigenetic events sound the DNA strand-breaks alarm to the ATM protein kinase. , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.

[127]  D. Durocher,et al.  DNA-PK, ATM and ATR as sensors of DNA damage: variations on a theme? , 2001, Current opinion in cell biology.

[128]  M. Kastan,et al.  ATM--a key determinant of multiple cellular responses to irradiation. , 2001, Acta oncologica.

[129]  A. Cuddihy,et al.  Inhibition of Chk1-dependent G2 DNA damage checkpoint radiosensitizes p53 mutant human cells , 2001, Oncogene.

[130]  B. Nelms,et al.  hMre11 and hRad50 nuclear foci are induced during the normal cellular response to DNA double-strand breaks , 1997, Molecular and cellular biology.

[131]  A. Kumagai,et al.  Requirement for Atr in phosphorylation of Chk1 and cell cycle regulation in response to DNA replication blocks and UV-damaged DNA in Xenopus egg extracts. , 2000, Genes & development.

[132]  S. Elledge,et al.  BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. , 2000, Genes & development.

[133]  M. Schneiderman,et al.  G2 Cells: Progression Delay and Survival1 , 1984 .

[134]  Y. Hosoi,et al.  Roles of DNA-dependent protein kinase and ATM in cell-cycle-dependent radiation sensitivity in human cells , 2002, International journal of radiation biology.

[135]  R. Bristow,et al.  The p53 gene as a modifier of intrinsic radiosensitivity: implications for radiotherapy. , 1996, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[136]  A. Howard,et al.  Synthesis of Desoxyribonucleic Acid in Normal and Irradiated Cells and Its Relation to Chromosome Breakage , 1986 .

[137]  E. Stanbridge,et al.  Complexity of the Mechanisms of Initiation and Maintenance of DNA Damage-Induced G2-Phase Arrest and Subsequent G1-Phase Arrest: TP53-Dependent and TP53-Independent Roles , 2003, Radiation research.

[138]  A. Hill,et al.  Lack of correlation between G1 arrest and radiation age-response in three synchronized human tumour cell lines. , 1999, International journal of radiation biology.

[139]  W. Dewey,et al.  Radiation-induced cycle delay in synchronized Chinese hamster cells: comparison between DNA synthesis and division. , 1973, Radiation research.

[140]  F. Collins,et al.  The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species. , 1995, Human molecular genetics.

[141]  P. Russell,et al.  Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein , 1999, Nature.

[142]  S. Schreiber,et al.  Overexpression of a kinase‐inactive ATR protein causes sensitivity to DNA‐damaging agents and defects in cell cycle checkpoints , 1998, The EMBO journal.

[143]  J. Little.  Delayed Initiation of DNA Synthesis in Irradiated Human Diploid Cells , 1968, Nature.

[144]  T. Coleman,et al.  Cdc2 regulatory factors. , 1994, Current opinion in cell biology.

[145]  E. Nishida,et al.  Plk1 promotes nuclear translocation of human Cdc25C during prophase , 2002, EMBO reports.

[146]  K. Valerie,et al.  Regulation and mechanisms of mammalian double-strand break repair , 2003, Oncogene.

[147]  Jun Qin,et al.  SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint. , 2002, Genes & development.

[148]  C. Deng,et al.  A targeted disruption of the murine Brca1 gene causes γ-irradiation hypersensitivity and genetic instability , 1998, Oncogene.

[149]  James M. Roberts,et al.  CDK inhibitors: positive and negative regulators of G1-phase progression. , 1999, Genes & development.

[150]  M. Itoh,et al.  Involvement of the Interaction between p21 and Proliferating Cell Nuclear Antigen for the Maintenance of G2/M Arrest after DNA Damage* , 2001, The Journal of Biological Chemistry.

[151]  Y Taya,et al.  The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. , 2000, Genes & development.

[152]  P. Dhar,et al.  Genetic Analysis of the DNA-dependent Protein Kinase Reveals an Inhibitory Role of Ku in Late S–G2 Phase DNA Double-strand Break Repair* , 2001, The Journal of Biological Chemistry.

[153]  R. S. St Onge,et al.  The human G2 checkpoint control protein hRAD9 is a nuclear phosphoprotein that forms complexes with hRAD1 and hHUS1. , 1999, Molecular biology of the cell.

[154]  P. Nurse,et al.  NOBEL LECTURE: Cyclin Dependent Kinases and Cell Cycle Control , 2002 .

[155]  Phang-lang Chen,et al.  The Nijmegen Breakage Syndrome Protein Is Essential for Mre11 Phosphorylation upon DNA Damage* , 1999, The Journal of Biological Chemistry.