WRN counteracts the NHEJ pathway upon camptothecin exposure

Makoto Otsuki; Masayuki Seki; Yoh ichi Kawabe; Eri Inoue; Yu Peng Dong; Takuya Abe; Genta Kato; Akari Yoshimura; Shusuke Tada; Takemi Enomoto

doi:10.1016/j.bbrc.2007.01.175

WRN counteracts the NHEJ pathway upon camptothecin exposure

Makoto Otsuki, Masayuki Seki, Yoh ichi Kawabe, Eri Inoue, Yu Peng Dong, Takuya Abe, Genta Kato, Akari Yoshimura, Shusuke Tada, Takemi Enomoto

研究成果: Article › 査読

19 被引用数 (Scopus)

抄録

We investigated the function of the interaction between WRN (Werner syndrome gene product) and Ku70 and between WRN and DNA-PKcs, which are components of the DNA-PKcs/Ku70/Ku80 complex, by generating KU70^-/-/WRN^-/- and DNA-PKcs^-/-/-/WRN^-/- double-gene knockout chicken DT40 cells. When treated with camptothecin (CPT), an inhibitor of DNA topoisomerase I, WRN^-/- cells showed higher sensitivity than wild-type cells, whereas KU70^-/- and DNA-PKcs^-/-/- cells showed hyper-resistance. Disruption of KU70 or DNA-PKcs suppressed the sensitivity of WRN^-/- cells to CPT, rendering them as resistant to CPT treatment as KU70^-/- and DNA-PKcs^-/-/- cells. On the other hand, CPT sensitivity of BLM^-/- cells, which are defective in a RecQ helicase similar to WRN, was enhanced by deletion of KU70. The implications for the function of WRN in the non-homologous end-joining pathway of DNA repair involving Ku70 and DNA-PKcs, which may be the cause of lethality in the presence of CPT, will be discussed.

本文言語	English
ページ（範囲）	477-482
ページ数	6
ジャーナル	Biochemical and biophysical research communications
巻	355
号	2
DOI	https://doi.org/10.1016/j.bbrc.2007.01.175
出版ステータス	Published - 2007 4月 6
外部発表	はい

ASJC Scopus subject areas

生物理学
生化学
分子生物学
細胞生物学

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10.1016/j.bbrc.2007.01.175

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@article{6f64c1e73a7e487a8a279f61a6c91a9a,

title = "WRN counteracts the NHEJ pathway upon camptothecin exposure",

abstract = "We investigated the function of the interaction between WRN (Werner syndrome gene product) and Ku70 and between WRN and DNA-PKcs, which are components of the DNA-PKcs/Ku70/Ku80 complex, by generating KU70-/-/WRN-/- and DNA-PKcs-/-/-/WRN-/- double-gene knockout chicken DT40 cells. When treated with camptothecin (CPT), an inhibitor of DNA topoisomerase I, WRN-/- cells showed higher sensitivity than wild-type cells, whereas KU70-/- and DNA-PKcs-/-/- cells showed hyper-resistance. Disruption of KU70 or DNA-PKcs suppressed the sensitivity of WRN-/- cells to CPT, rendering them as resistant to CPT treatment as KU70-/- and DNA-PKcs-/-/- cells. On the other hand, CPT sensitivity of BLM-/- cells, which are defective in a RecQ helicase similar to WRN, was enhanced by deletion of KU70. The implications for the function of WRN in the non-homologous end-joining pathway of DNA repair involving Ku70 and DNA-PKcs, which may be the cause of lethality in the presence of CPT, will be discussed.",

keywords = "BLM, CPT, DNA-PKcs, DT40, Etoposide, Ku70, PARP-1, RecQ, TopI, WRN",

author = "Makoto Otsuki and Masayuki Seki and Kawabe, {Yoh ichi} and Eri Inoue and Dong, {Yu Peng} and Takuya Abe and Genta Kato and Akari Yoshimura and Shusuke Tada and Takemi Enomoto",

note = "Funding Information: We thank Dr. S. Takeda for DT40 strains used in this study. We thank all members of Enomoto lab for their support. This work was supported by Grants-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports, and Culture of Japan. ",

year = "2007",

month = apr,

day = "6",

doi = "10.1016/j.bbrc.2007.01.175",

language = "English",

volume = "355",

pages = "477--482",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Academic Press Inc.",

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TY - JOUR

T1 - WRN counteracts the NHEJ pathway upon camptothecin exposure

AU - Otsuki, Makoto

AU - Seki, Masayuki

AU - Kawabe, Yoh ichi

AU - Inoue, Eri

AU - Dong, Yu Peng

AU - Abe, Takuya

AU - Kato, Genta

AU - Yoshimura, Akari

AU - Tada, Shusuke

AU - Enomoto, Takemi

N1 - Funding Information: We thank Dr. S. Takeda for DT40 strains used in this study. We thank all members of Enomoto lab for their support. This work was supported by Grants-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports, and Culture of Japan.

PY - 2007/4/6

Y1 - 2007/4/6

N2 - We investigated the function of the interaction between WRN (Werner syndrome gene product) and Ku70 and between WRN and DNA-PKcs, which are components of the DNA-PKcs/Ku70/Ku80 complex, by generating KU70-/-/WRN-/- and DNA-PKcs-/-/-/WRN-/- double-gene knockout chicken DT40 cells. When treated with camptothecin (CPT), an inhibitor of DNA topoisomerase I, WRN-/- cells showed higher sensitivity than wild-type cells, whereas KU70-/- and DNA-PKcs-/-/- cells showed hyper-resistance. Disruption of KU70 or DNA-PKcs suppressed the sensitivity of WRN-/- cells to CPT, rendering them as resistant to CPT treatment as KU70-/- and DNA-PKcs-/-/- cells. On the other hand, CPT sensitivity of BLM-/- cells, which are defective in a RecQ helicase similar to WRN, was enhanced by deletion of KU70. The implications for the function of WRN in the non-homologous end-joining pathway of DNA repair involving Ku70 and DNA-PKcs, which may be the cause of lethality in the presence of CPT, will be discussed.

AB - We investigated the function of the interaction between WRN (Werner syndrome gene product) and Ku70 and between WRN and DNA-PKcs, which are components of the DNA-PKcs/Ku70/Ku80 complex, by generating KU70-/-/WRN-/- and DNA-PKcs-/-/-/WRN-/- double-gene knockout chicken DT40 cells. When treated with camptothecin (CPT), an inhibitor of DNA topoisomerase I, WRN-/- cells showed higher sensitivity than wild-type cells, whereas KU70-/- and DNA-PKcs-/-/- cells showed hyper-resistance. Disruption of KU70 or DNA-PKcs suppressed the sensitivity of WRN-/- cells to CPT, rendering them as resistant to CPT treatment as KU70-/- and DNA-PKcs-/-/- cells. On the other hand, CPT sensitivity of BLM-/- cells, which are defective in a RecQ helicase similar to WRN, was enhanced by deletion of KU70. The implications for the function of WRN in the non-homologous end-joining pathway of DNA repair involving Ku70 and DNA-PKcs, which may be the cause of lethality in the presence of CPT, will be discussed.

KW - BLM

KW - CPT

KW - DNA-PKcs

KW - DT40

KW - Etoposide

KW - Ku70

KW - PARP-1

KW - RecQ

KW - TopI

KW - WRN

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U2 - 10.1016/j.bbrc.2007.01.175

DO - 10.1016/j.bbrc.2007.01.175

M3 - Article

C2 - 17303082

AN - SCOPUS:33847158810

SN - 0006-291X

VL - 355

SP - 477

EP - 482

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 2

ER -

WRN counteracts the NHEJ pathway upon camptothecin exposure

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