Parp-1 protects homologous recombination from interference by Ku and Ligase IV in vertebrate cells - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue EMBO Journal Année : 2006

Parp-1 protects homologous recombination from interference by Ku and Ligase IV in vertebrate cells

Helfrid Hochegger
Donniphat Dejsuphong
  • Fonction : Auteur
Toru Fukushima
  • Fonction : Auteur
Eiichiro Sonoda
  • Fonction : Auteur
Guang Yu Zhao
  • Fonction : Auteur
Alihossein Saberi
  • Fonction : Auteur
Mitsuko Masutani
  • Fonction : Auteur
Hideki Koyama
  • Fonction : Auteur
Shunichi Takeda
  • Fonction : Auteur

Résumé

Parp-1 and Parp-2 are activated by DNA breaks and have been implicated in the repair of DNA single-strand breaks (SSB). Their involvement in double-strand break (DSB) repair mediated by homologous recombination (HR) or nonhomologous end joining (NHEJ) remains unclear. We addressed this question using chicken DT40 cells, which have the advantage of carrying only a PARP-1 gene but not a PARP-2 gene. We found that PARP-1(-/-) DT40 mutants show reduced levels of HR and are sensitive to various DSB-inducing genotoxic agents. Surprisingly, this phenotype was strictly dependent on the presence of Ku, a DSB-binding factor that mediates NHEJ. PARP-1/KU70 double mutants were proficient in the execution of HR and displayed elevated resistance to DSB-inducing drugs. Moreover, we found deletion of Ligase IV, another NHEJ gene, suppressed the camptothecin of PARP-1(-/-) cells. Our results suggest a new critical function for Parp in minimizing the suppressive effects of Ku and the NHEJ pathway on HR.

Dates et versions

hal-02371528 , version 1 (19-11-2019)

Identifiants

Citer

Helfrid Hochegger, Donniphat Dejsuphong, Toru Fukushima, Ciaran Morrison, Eiichiro Sonoda, et al.. Parp-1 protects homologous recombination from interference by Ku and Ligase IV in vertebrate cells. EMBO Journal, 2006, 25 (6), pp.1305-14. ⟨10.1038/sj.emboj.7601015⟩. ⟨hal-02371528⟩
30 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More