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

Helfrid Hochegger; Donniphat Dejsuphong; Toru Fukushima; Ciaran Morrison; Eiichiro Sonoda; Valérie Schreiber; Yu Zhao Guang; Alihossein Saberi; Mitsuko Masutani; Noritaka Adachi; Hideki Koyama; Gilbert De Murcia; Shunichi Takeda

doi:10.1038/sj.emboj.7601015

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

Helfrid Hochegger
, Donniphat Dejsuphong
, Toru Fukushima
, Ciaran Morrison
, Eiichiro Sonoda
, Valérie Schreiber
, Yu Zhao Guang
, Alihossein Saberi
, Mitsuko Masutani
, Noritaka Adachi
, Hideki Koyama
, Gilbert De Murcia
, Shunichi Takeda

Molecular Biosciences

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

233 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1305-1314
Number of pages	10
Journal	EMBO Journal
Volume	25
Issue number	6
DOIs	https://doi.org/10.1038/sj.emboj.7601015
Publication status	Published - 22 Mar 2006

Keywords

Base excision repair
Camptothecin
Homologous recombination
Ionizing radiation
MMS

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10.1038/sj.emboj.7601015

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

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.",

keywords = "Base excision repair, Camptothecin, Homologous recombination, Ionizing radiation, MMS",

author = "Helfrid Hochegger and Donniphat Dejsuphong and Toru Fukushima and Ciaran Morrison and Eiichiro Sonoda and Val{\'e}rie Schreiber and Guang, \{Yu Zhao\} and Alihossein Saberi and Mitsuko Masutani and Noritaka Adachi and Hideki Koyama and \{De Murcia\}, Gilbert and Shunichi Takeda",

year = "2006",

month = mar,

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doi = "10.1038/sj.emboj.7601015",

language = "English",

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TY - JOUR

T1 - Parp-1 protects homologous recombination from interference by Ku and Ligase IV in vertebrate cells

AU - Hochegger, Helfrid

AU - Dejsuphong, Donniphat

AU - Fukushima, Toru

AU - Morrison, Ciaran

AU - Sonoda, Eiichiro

AU - Schreiber, Valérie

AU - Guang, Yu Zhao

AU - Saberi, Alihossein

AU - Masutani, Mitsuko

AU - Adachi, Noritaka

AU - Koyama, Hideki

AU - De Murcia, Gilbert

AU - Takeda, Shunichi

PY - 2006/3/22

Y1 - 2006/3/22

N2 - 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.

AB - 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.

KW - Base excision repair

KW - Camptothecin

KW - Homologous recombination

KW - Ionizing radiation

KW - MMS

UR - https://www.scopus.com/pages/publications/33645288259

U2 - 10.1038/sj.emboj.7601015

DO - 10.1038/sj.emboj.7601015

M3 - Article

SN - 0261-4189

VL - 25

SP - 1305

EP - 1314

JO - EMBO Journal

JF - EMBO Journal

IS - 6

ER -

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

Abstract

Keywords

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