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PMID: 12960401 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Intra-G1 arrest in response to UV irradiation in fission yeast.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 19 ·2003-09-16 ·Pages 10758-63

Nilssen EA, Synnes M, Kleckner N, Grallert B, Boye E

Abstract

G1 is a crucial phase of cell growth because the decision to begin another mitotic cycle is made during this period. Occurrence of DNA damage in G1 poses a particular challenge, because replication of damaged DNA can be deleterious and because no sister chromatid is present to provide a template for recombinational repair. We therefore have studied the response of Schizosaccharomyces pombe cells to UV irradiation in early G1 phase. We find that irradiation results in delayed progression through G1, as manifested most critically in the delayed formation of the pre-replication complex. This delay does not have the molecular hallmarks of known checkpoint responses: it is independent of the checkpoint proteins Rad3, Cds1, and Chk1 and does not elicit inhibitory phosphorylation of Cdc2. Irradiated cells eventually progress into S phase and arrest in early S by a rad3- and cds1-dependent mechanism, most likely the intra-S checkpoint. Caffeine alleviates both the intra-G1- and intra-S-phase delays. We suggest that intra-G1 delay may be widely conserved and discuss significance and possible mechanisms.

MeSH Terms
Adenosine Triphosphatases/metabolism Cell Cycle Proteins/metabolism Checkpoint Kinase 2 Chromatin/metabolism DNA Helicases/metabolism DNA-Binding Proteins/metabolism Flow Cytometry G1 Phase Gamma Rays Minichromosome Maintenance Complex Component 4 Phosphorylation Protein Kinases/metabolism Protein Serine-Threonine Kinases S Phase Saccharomyces cerevisiae Proteins/metabolism Schizosaccharomyces/cytology,metabolism,radiation effects Schizosaccharomyces pombe Proteins Ultraviolet Rays
Chemicals
Cell Cycle Proteins Chromatin DNA-Binding Proteins Saccharomyces cerevisiae Proteins Schizosaccharomyces pombe Proteins Protein Kinases Checkpoint Kinase 2 Cds1 protein, S pombe Protein Serine-Threonine Kinases Adenosine Triphosphatases Rad3 protein, S cerevisiae DNA Helicases MCM4 protein, S cerevisiae Minichromosome Maintenance Complex Component 4
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Nilssen Esben A
Department of Cell Biology, Institute for Cancer Research, Montebello, 0310 Oslo, Norway.
Synnes Marianne
Kleckner Nancy
Grallert Beáta
Boye Erik
References (56)
56 references, click to expand
  1. Mitochondrial growth and DNA synthesis occur in the absence of nuclear DNA replication in fission yeast.
    J Cell Sci. 1990 Nov;97 ( Pt 3):509-16 PMID: 2074269
  2. Evidence that a free-running oscillator drives G1 events in the budding yeast cell cycle.
    Nature. 1999 Sep 23;401(6751):394-7 PMID: 10517640
  3. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe.
    Methods Enzymol. 1991;194:795-823 PMID: 2005825
  4. Participation of p53 protein in the cellular response to DNA damage.
    Cancer Res. 1991 Dec 1;51(23 Pt 1):6304-11 PMID: 1933891
  5. Control of DNA synthesis genes in fission yeast by the cell-cycle gene cdc10+.
    Nature. 1992 Jan 30;355(6359):449-53 PMID: 1734281
  6. A new cdc gene required for S phase entry of Schizosaccharomyces pombe encodes a protein similar to the cdc 10+ and SWI4 gene products.
    EMBO J. 1992 Dec;11(13):4923-32 PMID: 1464317
  7. RAD9-dependent G1 arrest defines a second checkpoint for damaged DNA in the cell cycle of Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7985-9 PMID: 8367452
  8. Mutation in the bimD gene of Aspergillus nidulans confers a conditional mitotic block and sensitivity to DNA damaging agents.
    Genetics. 1993 Aug;134(4):1085-96 PMID: 8375649
  9. Characterization of G1 checkpoint control in the yeast Saccharomyces cerevisiae following exposure to DNA-damaging agents.
    Genetics. 1994 Oct;138(2):271-81 PMID: 7828811
  10. A kinase from fission yeast responsible for blocking mitosis in S phase.
    Nature. 1995 Apr 27;374(6525):817-9 PMID: 7723827
  11. A pre-start checkpoint preventing mitosis in fission yeast acts independently of p34cdc2 tyrosine phosphorylation.
    EMBO J. 1995 Jun 15;14(12):2760-71 PMID: 7796804
  12. Ataxia-telangiectasia and cellular responses to DNA damage.
    Cancer Res. 1995 Dec 15;55(24):5991-6001 PMID: 8521380
  13. A p53-independent damage-sensing mechanism that functions as a checkpoint at the G1/S transition in Chinese hamster ovary cells.
    Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):526-31 PMID: 9012817
  14. Chk1 is a wee1 kinase in the G2 DNA damage checkpoint inhibiting cdc2 by Y15 phosphorylation.
    EMBO J. 1997 Feb 3;16(3):545-54 PMID: 9034337
  15. Cdc2 tyrosine phosphorylation is required for the DNA damage checkpoint in fission yeast.
    Genes Dev. 1997 Feb 15;11(4):504-11 PMID: 9042863
  16. A direct link between sister chromatid cohesion and chromosome condensation revealed through the analysis of MCD1 in S. cerevisiae.
    Cell. 1997 Oct 3;91(1):47-57 PMID: 9335334
  17. Rad53-dependent phosphorylation of Swi6 and down-regulation of CLN1 and CLN2 transcription occur in response to DNA damage in Saccharomyces cerevisiae.
    Genes Dev. 1997 Nov 15;11(22):3032-45 PMID: 9367985
  18. Damage and replication checkpoint control in fission yeast is ensured by interactions of Crb2, a protein with BRCT motif, with Cut5 and Chk1.
    Genes Dev. 1997 Dec 15;11(24):3387-400 PMID: 9407031
  19. Ribosomal DNA replication in the fission yeast, Schizosaccharomyces pombe.
    Exp Cell Res. 1998 Jan 10;238(1):220-30 PMID: 9457075
  20. S-phase-specific activation of Cds1 kinase defines a subpathway of the checkpoint response in Schizosaccharomyces pombe.
    Genes Dev. 1998 Feb 1;12(3):382-95 PMID: 9450932
  21. The Schizosaccharomyces pombe S-phase checkpoint differentiates between different types of DNA damage.
    Genetics. 1998 Aug;149(4):1729-37 PMID: 9691032
  22. The Xenopus Chk1 protein kinase mediates a caffeine-sensitive pathway of checkpoint control in cell-free extracts.
    J Cell Biol. 1998 Sep 21;142(6):1559-69 PMID: 9744884
  23. Analysis of Rad3 and Chk1 protein kinases defines different checkpoint responses.
    EMBO J. 1998 Dec 15;17(24):7239-49 PMID: 9857181
  24. DNA damage and replication checkpoints in the fission yeast, Schizosaccharomyces pombe.
    Prog Nucleic Acid Res Mol Biol. 1999;62:369-95 PMID: 9932460
  25. Regulation of the start of DNA replication in Schizosaccharomyces pombe.
    J Cell Sci. 1999 Mar;112 ( Pt 6):939-46 PMID: 10036243
  26. DNA structure checkpoint pathways in Schizosaccharomyces pombe.
    Biochimie. 1999 Jan-Feb;81(1-2):173-81 PMID: 10214922
  27. Characterization of the components of the putative mammalian sister chromatid cohesion complex.
    Gene. 1999 Jun 11;233(1-2):39-47 PMID: 10375619
  28. Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis.
    Science. 1999 Jul 16;285(5426):418-22 PMID: 10411507
  29. Spo76p is a conserved chromosome morphogenesis protein that links the mitotic and meiotic programs.
    Cell. 1999 Jul 23;98(2):261-71 PMID: 10428037
  30. Cell cycle-regulated transcription in fission yeast: Cdc10-Res protein interactions during the cell cycle and domains required for regulated transcription.
    Mol Biol Cell. 1999 Nov;10(11):3705-15 PMID: 10564266
  31. An autonomous cell-cycle oscillator involved in the coordination of G1 events.
    Bioessays. 2000 Jan;22(1):3-5 PMID: 10649283
  32. Chromatin binding of the fission yeast replication factor mcm4 occurs during anaphase and requires ORC and cdc18.
    EMBO J. 2000 Apr 3;19(7):1681-90 PMID: 10747035
  33. Mechanism of caffeine-induced checkpoint override in fission yeast.
    Mol Cell Biol. 2000 Jun;20(12):4288-94 PMID: 10825192
  34. Replication of yeast rDNA initiates downstream of transcriptionally active genes.
    Mol Cell. 2000 May;5(5):767-77 PMID: 10882113
  35. A pcl-like cyclin activates the Res2p-Cdc10p cell cycle "start" transcriptional factor complex in fission yeast.
    Mol Biol Cell. 2000 Sep;11(9):2845-62 PMID: 10982385
  36. Reconstitution of an ATM-dependent checkpoint that inhibits chromosomal DNA replication following DNA damage.
    Mol Cell. 2000 Sep;6(3):649-59 PMID: 11030344
  37. The DNA damage response: putting checkpoints in perspective.
    Nature. 2000 Nov 23;408(6811):433-9 PMID: 11100718
  38. The many substrates and functions of ATM.
    Nat Rev Mol Cell Biol. 2000 Dec;1(3):179-86 PMID: 11252893
  39. BimD/SPO76 is at the interface of cell cycle progression, chromosome morphogenesis, and recombination.
    Proc Natl Acad Sci U S A. 2001 May 22;98(11):6267-72 PMID: 11353817
  40. ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1.
    Mol Cell Biol. 2001 Jul;21(13):4129-39 PMID: 11390642
  41. Serine-345 is required for Rad3-dependent phosphorylation and function of checkpoint kinase Chk1 in fission yeast.
    Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11289-94 PMID: 11553781
  42. Regulation of replication timing in fission yeast.
    EMBO J. 2001 Nov 1;20(21):6115-26 PMID: 11689451
  43. Mrc1 transduces signals of DNA replication stress to activate Rad53.
    Nat Cell Biol. 2001 Nov;3(11):958-65 PMID: 11715016
  44. Mrc1 channels the DNA replication arrest signal to checkpoint kinase Cds1.
    Nat Cell Biol. 2001 Nov;3(11):966-72 PMID: 11715017
  45. Robust G1 checkpoint arrest in budding yeast: dependence on DNA damage signaling and repair.
    J Cell Sci. 2002 Apr 15;115(Pt 8):1749-57 PMID: 11950891
  46. G(1)/S CDK is inhibited to restrain mitotic onset when DNA replication is blocked in fission yeast.
    EMBO J. 2002 Jul 1;21(13):3370-6 PMID: 12093738
  47. ATR homolog Mec1 promotes fork progression, thus averting breaks in replication slow zones.
    Science. 2002 Jul 26;297(5581):602-6 PMID: 12142538
  48. Rad53 checkpoint kinase phosphorylation site preference identified in the Swi6 protein of Saccharomyces cerevisiae.
    Mol Cell Biol. 2003 May;23(10):3405-16 PMID: 12724400
  49. Caffeine inhibits checkpoint responses without inhibiting the ataxia-telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR) protein kinases.
    J Biol Chem. 2003 Sep 26;278(39):37139-45 PMID: 12847089
  50. The action of caffeine on X-irradiated HeLa cells. I. Delayed inhibition of DNA synthesis.
    Radiat Res. 1977 Sep;71(3):653-65 PMID: 897091
  51. Gene required in G1 for commitment to cell cycle and in G2 for control of mitosis in fission yeast.
    Nature. 1981 Aug 6;292(5823):558-60 PMID: 7254352
  52. Cloning, sequencing and transcriptional control of the Schizosaccharomyces pombe cdc10 'start' gene.
    EMBO J. 1985 Feb;4(2):457-63 PMID: 4018034
  53. Checkpoints: controls that ensure the order of cell cycle events.
    Science. 1989 Nov 3;246(4930):629-34 PMID: 2683079
  54. Heterogeneity in radiation-induced DNA damage and repair in tumor and normal cells measured using the "comet" assay.
    Radiat Res. 1990 Apr;122(1):86-94 PMID: 2320728
  55. Cell cycle progression in the presence of irreparable DNA damage is controlled by a Mec1- and Rad53-dependent checkpoint in budding yeast.
    EMBO J. 1999 Aug 16;18(16):4485-97 PMID: 10449414
  56. mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2.
    Cell. 1991 Mar 22;64(6):1111-22 PMID: 1706223
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.1833769100
Published
2003-09-16
Epub
2003-00-05
Pages
10758-63
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC196876
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.1833769100 PMC Full Text View journal details
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