Redundancy, insult-specific sensors and thresholds: unlocking the S-phase checkpoint response.

DNA damage that is not properly repaired during genomic replication is a major source of gross chromosomal rearrangements and sequence loss during cell proliferation. In higher eukaryotes such mutations increase the risk of cancer. Eukaryotic cells have multiple checkpoint responses activated by DNA damage and stalled replication forks. We focus here on fork-associated events that activate and respond to S-phase checkpoint kinases.

[1]  Stephen J. Elledge,et al.  Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes , 2003, Science.

[2]  D. J. Clarke,et al.  Dosage Suppressors of pds1 Implicate Ubiquitin-Associated Domains in Checkpoint Control , 2001, Molecular and Cellular Biology.

[3]  N. Kleckner,et al.  ATR Homolog Mec1 Promotes Fork Progression, Thus Averting Breaks in Replication Slow Zones , 2002, Science.

[4]  Georges Mer,et al.  The BRCT Domain Is a Phospho-Protein Binding Domain , 2003, Science.

[5]  Robin C. Allshire,et al.  Hsk1–Dfp1 is required for heterochromatin-mediated cohesion at centromeres , 2003, Nature Cell Biology.

[6]  Caroline M. Li,et al.  Saccharomyces cerevisiae DNA Polymerase ε and Polymerase σ Interact Physically and Functionally, Suggesting a Role for Polymerase ε in Sister Chromatid Cohesion , 2003, Molecular and Cellular Biology.

[7]  Michael B Yaffe,et al.  BRCT Repeats As Phosphopeptide-Binding Modules Involved in Protein Targeting , 2003, Science.

[8]  D. J. Clarke,et al.  Mec1p regulates Pds1p levels in S phase: complex coordination of DNA replication and mitosis , 2001, Nature Cell Biology.

[9]  Kunihiro Matsumoto,et al.  ATM-related Tel1 associates with double-strand breaks through an Xrs2-dependent mechanism. , 2003, Genes & development.

[10]  Kim Nasmyth,et al.  Segregating Sister Genomes: The Molecular Biology of Chromosome Separation , 2002, Science.

[11]  M. Christman,et al.  Pol κ: A DNA Polymerase Required for Sister Chromatid Cohesion , 2000 .

[12]  Kunihiro Matsumoto,et al.  The ATM-related Tel1 protein of Saccharomyces cerevisiae controls a checkpoint response following phleomycin treatment. , 2003, Nucleic acids research.

[13]  Monika Tsai-Pflugfelder,et al.  An N-terminal domain of Dbf4p mediates interaction with both origin recognition complex (ORC) and Rad53p and can deregulate late origin firing , 2002, Proceedings of the National Academy of Sciences of the United States of America.

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

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

[16]  S. Jackson,et al.  The yeast Xrs2 complex functions in S phase checkpoint regulation. , 2001, Genes & development.

[17]  Junjie Chen,et al.  MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways , 2003, Nature.

[18]  D. Stern,et al.  FHA Domain-Mediated DNA Checkpoint Regulation of Rad53 , 2003, Cell cycle.

[19]  C. Newlon,et al.  The DNA replication checkpoint response stabilizes stalled replication forks , 2001, Nature.

[20]  J. Haber,et al.  Regulation of Saccharomyces Rad53 checkpoint kinase during adaptation from DNA damage-induced G2/M arrest. , 2001, Molecular cell.

[21]  M. Kenna,et al.  Mechanical Link between Cohesion Establishment and DNA Replication: Ctf7p/Eco1p, a Cohesion Establishment Factor, Associates with Three Different Replication Factor C Complexes , 2003, Molecular and Cellular Biology.

[22]  Georges Mer,et al.  The BRCT Domain Is a PhosphoProtein Binding Domain , 2022 .

[23]  Stephen J. Elledge,et al.  Mrc1 transduces signals of DNA replication stress to activate Rad53 , 2001, Nature Cell Biology.

[24]  Kim Nasmyth,et al.  An ESP1/PDS1 Complex Regulates Loss of Sister Chromatid Cohesion at the Metaphase to Anaphase Transition in Yeast , 1998, Cell.

[25]  S. Gygi,et al.  Identification of RFC(Ctf18p, Ctf8p, Dcc1p): an alternative RFC complex required for sister chromatid cohesion in S. cerevisiae. , 2001, Molecular cell.

[26]  P. Russell,et al.  Replication Checkpoint Protein Mrc1 Is Regulated by Rad3 and Tel1 in Fission Yeast , 2003, Molecular and Cellular Biology.

[27]  S. Elledge,et al.  Mrc1 is a replication fork component whose phosphorylation in response to DNA replication stress activates Rad53. , 2003, Genes & development.

[28]  J. Haber,et al.  Saccharomyces Ku70, Mre11/Rad50, and RPA Proteins Regulate Adaptation to G2/M Arrest after DNA Damage , 1998, Cell.

[29]  A. Carr,et al.  A single unbranched S-phase DNA damage and replication fork blockage checkpoint pathway , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[30]  J. Haber,et al.  Checkpoint-mediated control of replisome–fork association and signalling in response to replication pausing , 2004, Oncogene.

[31]  S. Elledge,et al.  The mitotic spindle is required for loading of the DASH complex onto the kinetochore. , 2002, Genes & development.

[32]  S. Gasser,et al.  DNA polymerase stabilization at stalled replication forks requires Mec1 and the RecQ helicase Sgs1 , 2003, The EMBO journal.

[33]  M. Lopes,et al.  Fork Reversal and ssDNA Accumulation at Stalled Replication Forks Owing to Checkpoint Defects , 2002, Science.

[34]  P. Russell,et al.  Swi1 Prevents Replication Fork Collapse and Controls Checkpoint Kinase Cds1 , 2003, Molecular and Cellular Biology.

[35]  M. Christman,et al.  Pol kappa: A DNA polymerase required for sister chromatid cohesion. , 2000, Science.

[36]  J. Diffley,et al.  A central role for DNA replication forks in checkpoint activation and response. , 2003, Molecular cell.

[37]  G. Lucchini,et al.  Characterization of mec1Kinase-Deficient Mutants and of New Hypomorphic mec1Alleles Impairing Subsets of the DNA Damage Response Pathway , 2001, Molecular and Cellular Biology.

[38]  J. Haber,et al.  Recovery from checkpoint-mediated arrest after repair of a double-strand break requires Srs2 helicase. , 2002, Molecular cell.

[39]  P. Russell,et al.  Mrc1 channels the DNA replication arrest signal to checkpoint kinase Cds1 , 2001, Nature Cell Biology.

[40]  S. Elledge,et al.  The DASH Complex Component Ask1 Is a Cell Cycle-Regulated Cdk Substrate in Saccharomyces cerevisiae , 2003, Cell cycle.

[41]  Kenji Shimada,et al.  Multiple Roles of Replication Forks in S Phase Checkpoints: Sensors, Effectors and Targets , 2003, Cell cycle.

[42]  E. Foss Tof1p regulates DNA damage responses during S phase in Saccharomyces cerevisiae. , 2001, Genetics.

[43]  S. Gasser,et al.  ORC and the intra-S-phase checkpoint: a threshold regulates Rad53p activation in S phase. , 2002, Genes & development.

[44]  J. Gautier,et al.  An ATR- and Cdc7-dependent DNA damage checkpoint that inhibits initiation of DNA replication. , 2003, Molecular cell.

[45]  J. Bartek,et al.  The DNA damage-dependent intra–S phase checkpoint is regulated by parallel pathways , 2002, Nature Genetics.

[46]  F. Spencer,et al.  Saccharomyces cerevisiae CTF18 and CTF4 Are Required for Sister Chromatid Cohesion , 2001, Molecular and Cellular Biology.

[47]  W. Dunphy,et al.  Xenopus Drf1, a Regulator of Cdc7, Displays Checkpoint-dependent Accumulation on Chromatin during an S-phase Arrest* , 2003, Journal of Biological Chemistry.

[48]  J. Bartek,et al.  MDC1 is required for the intra-S-phase DNA damage checkpoint , 2003, Nature.

[49]  Hiroyuki Araki,et al.  Dpb11 Controls the Association between DNA Polymerases α and ɛ and the Autonomously Replicating Sequence Region of Budding Yeast , 2000, Molecular and Cellular Biology.

[50]  S. Brill,et al.  Rfc4 Interacts with Rpa1 and Is Required for Both DNA Replication and DNA Damage Checkpoints in Saccharomyces cerevisiae , 2001, Molecular and Cellular Biology.

[51]  Brian D. Peyser,et al.  S-phase checkpoint genes safeguard high-fidelity sister chromatid cohesion. , 2004, Molecular biology of the cell.

[52]  Grant W. Brown,et al.  Identification of protein complexes required for efficient sister chromatid cohesion. , 2004, Molecular biology of the cell.

[53]  J. Diffley,et al.  Regulation of DNA replication fork progression through damaged DNA by the Mec1/Rad53 checkpoint , 2001, Nature.

[54]  D. J. Clarke,et al.  S-phase checkpoint controls mitosis via an APC-independent Cdc20p function , 2003, Nature Cell Biology.

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

[56]  R. Allshire,et al.  Requirement of Heterochromatin for Cohesion at Centromeres , 2001, Science.

[57]  D. J. Clarke,et al.  UBA domains of DNA damage-inducible proteins interact with ubiquitin , 2001, Nature Structural Biology.

[58]  Katsuhiko Shirahige,et al.  S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex , 2003, Nature.

[59]  T. Kitajima,et al.  Recruitment of cohesin to heterochromatic regions by Swi6/HP1 in fission yeast , 2002, Nature Cell Biology.