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PMID: 15549137 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The CDK regulates repair of double-strand breaks by homologous recombination during the cell cycle.

The EMBO journal ·Vol. 23 ·No. 24 ·2004-12-08 ·Pages 4868-75

Aylon Y, Liefshitz B, Kupiec M

Abstract

DNA double-strand breaks (DSBs) are dangerous lesions that can lead to genomic instability and cell death. Eukaryotic cells repair DSBs either by nonhomologous end-joining (NHEJ) or by homologous recombination. We investigated the ability of yeast cells (Saccharomyces cerevisiae) to repair a single, chromosomal DSB by recombination at different stages of the cell cycle. We show that cells arrested at the G1 phase of the cell cycle restrict homologous recombination, but are able to repair the DSB by NHEJ. Furthermore, we demonstrate that recombination ability does not require duplicated chromatids or passage through S phase, and is controlled at the resection step by Clb-CDK activity.

MeSH Terms
Animals Cell Cycle/physiology Cyclin-Dependent Kinases/genetics,metabolism DNA Damage DNA Repair Recombination, Genetic Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism
Chemicals
Saccharomyces cerevisiae Proteins Cyclin-Dependent Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Aylon Yael
Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv, Israel.
Liefshitz Batia
Kupiec Martin
References (25)
25 references, click to expand
  1. Activation of Rad53 kinase in response to DNA damage and its effect in modulating phosphorylation of the lagging strand DNA polymerase.
    EMBO J. 1999 Nov 15;18(22):6561-72 PMID: 10562568
  2. Cdc4, a protein required for the onset of S phase, serves an essential function during G(2)/M transition in Saccharomyces cerevisiae.
    Mol Cell Biol. 1999 Aug;19(8):5512-22 PMID: 10409741
  3. Regulation of Saccharomyces Rad53 checkpoint kinase during adaptation from DNA damage-induced G2/M arrest.
    Mol Cell. 2001 Feb;7(2):293-300 PMID: 11239458
  4. Two checkpoint complexes are independently recruited to sites of DNA damage in vivo.
    Genes Dev. 2001 Nov 1;15(21):2809-21 PMID: 11691833
  5. The yeast CDK inhibitor Sic1 prevents genomic instability by promoting replication origin licensing in late G(1).
    Mol Cell. 2002 May;9(5):1067-78 PMID: 12049742
  6. Maintenance of genome stability in Saccharomyces cerevisiae.
    Science. 2002 Jul 26;297(5581):552-7 PMID: 12142524
  7. Transient stability of DNA ends allows nonhomologous end joining to precede homologous recombination.
    Mol Cell. 2002 Nov;10(5):1189-99 PMID: 12453425
  8. Molecular dissection of mitotic recombination in the yeast Saccharomyces cerevisiae.
    Mol Cell Biol. 2003 Feb;23(4):1403-17 PMID: 12556499
  9. A central role for DNA replication forks in checkpoint activation and response.
    Mol Cell. 2003 May;11(5):1323-36 PMID: 12769855
  10. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes.
    Science. 2003 Jun 6;300(5625):1542-8 PMID: 12791985
  11. The checkpoint protein Rad24 of Saccharomyces cerevisiae is involved in processing double-strand break ends and in recombination partner choice.
    Mol Cell Biol. 2003 Sep;23(18):6585-96 PMID: 12944484
  12. Hydroxyurea arrests DNA replication by a mechanism that preserves basal dNTP pools.
    J Biol Chem. 2004 Jan 2;279(1):223-30 PMID: 14573610
  13. Gene conversion at different points in the mitotic cycle of Saccharomyces cerevisiae.
    Mol Gen Genet. 1984;195(1-2):139-43 PMID: 6387388
  14. An inhibitor of p34CDC28 protein kinase activity from Saccharomyces cerevisiae.
    Science. 1993 Jan 8;259(5092):216-9 PMID: 8421781
  15. Comparison of the Saccharomyces cerevisiae G1 cyclins: Cln3 may be an upstream activator of Cln1, Cln2 and other cyclins.
    EMBO J. 1993 May;12(5):1955-68 PMID: 8387915
  16. Control of the yeast cell cycle by the Cdc28 protein kinase.
    Curr Opin Cell Biol. 1993 Apr;5(2):166-79 PMID: 8507488
  17. Joining the complex: cyclin-dependent kinase inhibitory proteins and the cell cycle.
    Cell. 1994 Oct 21;79(2):181-4 PMID: 7954786
  18. Identification of Saccharomyces cerevisiae DNA ligase IV: involvement in DNA double-strand break repair.
    EMBO J. 1997 Aug 1;16(15):4788-95 PMID: 9303323
  19. RAD9 and RAD24 define two additive, interacting branches of the DNA damage checkpoint pathway in budding yeast normally required for Rad53 modification and activation.
    EMBO J. 1998 May 1;17(9):2687-98 PMID: 9564050
  20. Effects of DNA double-strand and single-strand breaks on intrachromosomal recombination events in cell-cycle-arrested yeast cells.
    Genetics. 1998 Jul;149(3):1235-50 PMID: 9649517
  21. 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.
    EMBO J. 1998 Sep 15;17(18):5497-508 PMID: 9736627
  22. Mating-type gene switching in Saccharomyces cerevisiae.
    Annu Rev Genet. 1998;32:561-99 PMID: 9928492
  23. Homology search and choice of homologous partner during mitotic recombination.
    Mol Cell Biol. 1999 Jun;19(6):4134-42 PMID: 10330153
  24. Perspective: defects in cell cycle control and cancer.
    J Pathol. 1999 Jan;187(1):95-9 PMID: 10341710
  25. The nonhomologous end-joining pathway of DNA repair is required for genomic stability and the suppression of translocations.
    Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6630-3 PMID: 10823907
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
2004-12-08
Epub
2004-00-18
Pages
4868-75
Language
English
Region
England
NLM ID
8208664
PMCID
PMC535085
Subset
IM
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