Home LiteratureArticle Details
PMID: 19103807 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

PARP-1 ensures regulation of replication fork progression by homologous recombination on damaged DNA.

The Journal of cell biology ·Vol. 183 ·No. 7 ·2008-12-29 ·Pages 1203-12

Sugimura K, Takebayashi S, Taguchi H, Takeda S, Okumura K

Abstract

Poly-ADP ribose polymerase 1 (PARP-1) is activated by DNA damage and has been implicated in the repair of single-strand breaks (SSBs). Involvement of PARP-1 in other DNA damage responses remains controversial. In this study, we show that PARP-1 is required for replication fork slowing on damaged DNA. Fork progression in PARP-1(-/-) DT40 cells is not slowed down even in the presence of DNA damage induced by the topoisomerase I inhibitor camptothecin (CPT). Mammalian cells treated with a PARP inhibitor or PARP-1-specific small interfering RNAs show similar results. The expression of human PARP-1 restores fork slowing in PARP-1(-/-) DT40 cells. PARP-1 affects SSB repair, homologous recombination (HR), and nonhomologous end joining; therefore, we analyzed the effect of CPT on DT40 clones deficient in these pathways. We find that fork slowing is correlated with the proficiency of HR-mediated repair. Our data support the presence of a novel checkpoint pathway in which the initiation of HR but not DNA damage delays the fork progression.

MeSH Terms
Animals COS Cells Camptothecin/pharmacology Cells, Cultured Chlorocebus aethiops DNA Breaks, Double-Stranded/drug effects DNA Damage/genetics,physiology DNA Replication HeLa Cells Humans Poly (ADP-Ribose) Polymerase-1 Poly(ADP-ribose) Polymerases/analysis,genetics,metabolism Recombination, Genetic
Chemicals
PARP1 protein, human Poly (ADP-Ribose) Polymerase-1 Poly(ADP-ribose) Polymerases Camptothecin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Sugimura Kazuto
Department of Life Science, Graduate School of Bioresources, Mie University, Tsu, Mie 514-8507, Japan. [email protected]
Takebayashi Shin-Ichiro
Taguchi Hiroshi
Takeda Shunichi
Okumura Katsuzumi
References (29)
29 references, click to expand
  1. Differential effects of the poly (ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro.
    Br J Cancer. 2001 Jan 5;84(1):106-12 PMID: 11139322
  2. Homologous and non-homologous recombination differentially affect DNA damage repair in mice.
    EMBO J. 2000 Apr 3;19(7):1703-10 PMID: 10747037
  3. Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1.
    Nature. 2005 Mar 3;434(7029):108-13 PMID: 15744309
  4. Establishment and some mutational characteristics of 3T3-like near-diploid mouse cell line.
    J Cell Physiol. 1987 Apr;131(1):114-22 PMID: 3571334
  5. Poly(ADP-ribose) polymerase and Ku autoantigen form a complex and synergistically bind to matrix attachment sequences.
    J Biol Chem. 1999 Jul 16;274(29):20521-8 PMID: 10400681
  6. Poly(ADP-ribosyl)ation as a DNA damage-induced post-translational modification regulating poly(ADP-ribose) polymerase-1-topoisomerase I interaction.
    J Biol Chem. 2004 Sep 17;279(38):39686-96 PMID: 15247263
  7. Camptothecin hypersensitivity in poly(adenosine diphosphate-ribose) polymerase-deficient cell lines.
    Cancer Commun. 1989;1(6):389-94 PMID: 2562007
  8. Physical and functional interaction between DNA ligase IIIalpha and poly(ADP-Ribose) polymerase 1 in DNA single-strand break repair.
    Mol Cell Biol. 2003 Aug;23(16):5919-27 PMID: 12897160
  9. Parp-1 protects homologous recombination from interference by Ku and Ligase IV in vertebrate cells.
    EMBO J. 2006 Mar 22;25(6):1305-14 PMID: 16498404
  10. Functional association of poly(ADP-ribose) polymerase with DNA polymerase alpha-primase complex: a link between DNA strand break detection and DNA replication.
    Nucleic Acids Res. 1998 Apr 15;26(8):1891-8 PMID: 9518481
  11. Similar effects of Brca2 truncation and Rad51 paralog deficiency on immunoglobulin V gene diversification in DT40 cells support an early role for Rad51 paralogs in homologous recombination.
    Mol Cell Biol. 2005 Feb;25(3):1124-34 PMID: 15657438
  12. Dynamic molecular combing: stretching the whole human genome for high-resolution studies.
    Science. 1997 Sep 5;277(5331):1518-23 PMID: 9278517
  13. XRCC1 polypeptide interacts with DNA polymerase beta and possibly poly (ADP-ribose) polymerase, and DNA ligase III is a novel molecular 'nick-sensor' in vitro.
    Nucleic Acids Res. 1996 Nov 15;24(22):4387-94 PMID: 8948628
  14. Suppression of the poly(ADP-ribose) polymerase activity by DNA-dependent protein kinase in vitro.
    Oncogene. 1999 Aug 12;18(32):4616-25 PMID: 10467406
  15. RNA interference directed against Poly(ADP-Ribose) polymerase 1 efficiently suppresses human immunodeficiency virus type 1 replication in human cells.
    J Virol. 2004 Aug;78(16):8931-4 PMID: 15280503
  16. Replication fork reactivation downstream of a blocked nascent leading strand.
    Nature. 2006 Feb 2;439(7076):557-62 PMID: 16452972
  17. DNA double-strand breaks associated with replication forks are predominantly repaired by homologous recombination involving an exchange mechanism in mammalian cells.
    J Mol Biol. 2001 Apr 13;307(5):1235-45 PMID: 11292338
  18. Human proliferating cell nuclear antigen, poly(ADP-ribose) polymerase-1, and p21waf1/cip1. A dynamic exchange of partners.
    J Biol Chem. 2003 Oct 10;278(41):39265-8 PMID: 12930846
  19. XRCC3 and Rad51 modulate replication fork progression on damaged vertebrate chromosomes.
    Mol Cell. 2003 Apr;11(4):1109-17 PMID: 12718895
  20. Antitumour drugs impede DNA uncoiling by topoisomerase I.
    Nature. 2007 Jul 12;448(7150):213-7 PMID: 17589503
  21. Identification and biochemical characterization of a Werner's syndrome protein complex with Ku70/80 and poly(ADP-ribose) polymerase-1.
    J Biol Chem. 2004 Apr 2;279(14):13659-67 PMID: 14734561
  22. 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
  23. A new XRCC1-containing complex and its role in cellular survival of methyl methanesulfonate treatment.
    Mol Cell Biol. 2004 Oct;24(19):8356-65 PMID: 15367657
  24. Association of XRCC1 and tyrosyl DNA phosphodiesterase (Tdp1) for the repair of topoisomerase I-mediated DNA lesions.
    DNA Repair (Amst). 2003 Oct 7;2(10):1087-100 PMID: 13679147
  25. Involvement of Hus1 in the chain elongation step of DNA replication after exposure to camptothecin or ionizing radiation.
    Nucleic Acids Res. 2004 Feb 03;32(2):767-75 PMID: 14762204
  26. XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively regulates its activity following DNA damage.
    Mol Cell Biol. 1998 Jun;18(6):3563-71 PMID: 9584196
  27. Repair of and checkpoint response to topoisomerase I-mediated DNA damage.
    Mutat Res. 2003 Nov 27;532(1-2):173-203 PMID: 14643436
  28. The effect of Hus1 on ionizing radiation sensitivity is associated with homologous recombination repair but is independent of nonhomologous end-joining.
    Oncogene. 2006 Mar 23;25(13):1980-3 PMID: 16278671
  29. A positive role for the Ku complex in DNA replication following strand break damage in mammals.
    J Biol Chem. 2004 Feb 13;279(7):6046-55 PMID: 14617623
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200806068
Email
[email protected]
Published
2008-12-29
Epub
2008-00-22
Pages
1203-12
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2606964
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200806068 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2