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Parp-1 protects homologous recombination from interference by ku and ligase iv in vertebrate cells

Hochegger, Helfrid
; 
Dejsuphong, Donniphat
; 
Fukushima, Toru
; 
Morrison, Ciaran
; 
Sonoda, Eiichiro
; 
Schreiber, Valérie
; 
Zhao, Guang Yu
; 
Saberi, Alihossein
; 
Masutani, Mitsuko
; 
Adachi, Noritaka
... show 3 more
Identifiers
http://hdl.handle.net/10379/9307
 https://doi.org/10.13025/24070
Publication Date
2006-02-23
Keywords
base excision repair, camptothecin, homologous recombination, ionizing radiation, mms, strand break repair, poly(adp-ribose) polymerase-2 parp-2, sister-chromatid exchanges, mediated DNA-damage, mammalian-cells, topoisomerase-i, functional interaction, v(d)j recombination, gene-disruption, mice
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Article
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Citation
Hochegger, Helfrid; Dejsuphong, Donniphat; Fukushima, Toru; Morrison, Ciaran; Sonoda, Eiichiro; Schreiber, Valérie; Zhao, Guang Yu; Saberi, Alihossein; Masutani, Mitsuko; Adachi, Noritaka; Koyama, Hideki; de Murcia, Gilbert; Takeda, Shunichi (2006). Parp-1 protects homologous recombination from interference by ku and ligase iv in vertebrate cells. The EMBO Journal 25 (6), 1305-1314
Abstract
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.
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Publisher
Wiley-Blackwell
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Attribution-NonCommercial-NoDerivs 3.0 Ireland
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Externally hosted open access publications with University of Galway authors (1)