Mouse DNA polymerase kappa has a functional role in the repair of DNA strand breaks

Xiuli Zhang; Lingna Lv; Qian Chen; Fenghua Yuan; Ting Zhang; Yeran Yang; Hui Zhang; Yun Wang; Yan Jia; Liangyue Qian; Benjamin Chen; Yanbin Zhang; Errol C. Friedberg; Tie Shan Tang; Caixia Guo

doi:10.1016/j.dnarep.2013.02.008

Mouse DNA polymerase kappa has a functional role in the repair of DNA strand breaks

Xiuli Zhang, Lingna Lv, Qian Chen, Fenghua Yuan, Ting Zhang, Yeran Yang, Hui Zhang, Yun Wang, Yan Jia, Liangyue Qian, Benjamin Chen, Yanbin Zhang, Errol C. Friedberg, Tie Shan Tang, Caixia Guo

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

The Y-family of DNA polymerases support of translesion DNA synthesis (TLS) associated with stalled DNA replication by DNA damage. Recently, a number of studies suggest that some specialized TLS polymerases also support other aspects of DNA metabolism beyond TLS in vivo. Here we show that mouse polymerase kappa (Polκ) could accumulate at laser-induced sites of damage in vivo resembling polymerases eta and iota. The recruitment was mediated through Polκ C-terminus which contains the PCNA-interacting peptide, ubiquitin zinc finger motif 2 and nuclear localization signal. Interestingly, this recruitment was significantly reduced in MSH2-deficient LoVo cells and Rad18-depleted cells. We further observed that Polκ-deficient mouse embryo fibroblasts were abnormally sensitive to H₂O₂ treatment and displayed defects in both single-strand break repair and double-strand break repair. We speculate that Polκ may have an important role in strand break repair following oxidative stress in vivo.

Original language	English (US)
Pages (from-to)	377-388
Number of pages	12
Journal	DNA repair
Volume	12
Issue number	5
DOIs	https://doi.org/10.1016/j.dnarep.2013.02.008
State	Published - May 1 2013

Keywords

Laser micro-irradiation
MSH2
PCNA
Polymerase kappa
Strand break repair

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.dnarep.2013.02.008

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@article{c934f178769c4b0db8dd4a73f105f0d0,

title = "Mouse DNA polymerase kappa has a functional role in the repair of DNA strand breaks",

abstract = "The Y-family of DNA polymerases support of translesion DNA synthesis (TLS) associated with stalled DNA replication by DNA damage. Recently, a number of studies suggest that some specialized TLS polymerases also support other aspects of DNA metabolism beyond TLS in vivo. Here we show that mouse polymerase kappa (Polκ) could accumulate at laser-induced sites of damage in vivo resembling polymerases eta and iota. The recruitment was mediated through Polκ C-terminus which contains the PCNA-interacting peptide, ubiquitin zinc finger motif 2 and nuclear localization signal. Interestingly, this recruitment was significantly reduced in MSH2-deficient LoVo cells and Rad18-depleted cells. We further observed that Polκ-deficient mouse embryo fibroblasts were abnormally sensitive to H2O2 treatment and displayed defects in both single-strand break repair and double-strand break repair. We speculate that Polκ may have an important role in strand break repair following oxidative stress in vivo.",

keywords = "Laser micro-irradiation, MSH2, PCNA, Polymerase kappa, Strand break repair",

author = "Xiuli Zhang and Lingna Lv and Qian Chen and Fenghua Yuan and Ting Zhang and Yeran Yang and Hui Zhang and Yun Wang and Yan Jia and Liangyue Qian and Benjamin Chen and Yanbin Zhang and Friedberg, {Errol C.} and Tang, {Tie Shan} and Caixia Guo",

note = "Funding Information: The authors thank Drs. Alan Lehmann, David Chen and Haiying Hang for cells and plasmids, Dr. Akira Yasui for helpful discussions, Shiya Wang and Ana Doughty for help with initial micro-irradiation and Min Huang for preparing plasmids. This work was supported by grants 2011CB944302 , 2013CB945000 and 2012CB944702 ( 973 Program ), 30970588 and 31170730 ( NSFC ) (C.G), R01HL105631 ( NIH ) (Y.Z), 30970931 (NSFC) (T.T), KSCX2-YW-R-148 ( the Knowledge Innovation Program of Chinese Academy of Sciences ), 31100557 (NSFC) (H.Z), and the Chinese Academy of Sciences “One-Hundred-Talent Program” (C.G). ",

year = "2013",

month = may,

day = "1",

doi = "10.1016/j.dnarep.2013.02.008",

language = "English (US)",

volume = "12",

pages = "377--388",

journal = "DNA repair",

issn = "1568-7864",

publisher = "Elsevier",

number = "5",

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TY - JOUR

T1 - Mouse DNA polymerase kappa has a functional role in the repair of DNA strand breaks

AU - Zhang, Xiuli

AU - Lv, Lingna

AU - Chen, Qian

AU - Yuan, Fenghua

AU - Zhang, Ting

AU - Yang, Yeran

AU - Zhang, Hui

AU - Wang, Yun

AU - Jia, Yan

AU - Qian, Liangyue

AU - Chen, Benjamin

AU - Zhang, Yanbin

AU - Friedberg, Errol C.

AU - Tang, Tie Shan

AU - Guo, Caixia

N1 - Funding Information: The authors thank Drs. Alan Lehmann, David Chen and Haiying Hang for cells and plasmids, Dr. Akira Yasui for helpful discussions, Shiya Wang and Ana Doughty for help with initial micro-irradiation and Min Huang for preparing plasmids. This work was supported by grants 2011CB944302 , 2013CB945000 and 2012CB944702 ( 973 Program ), 30970588 and 31170730 ( NSFC ) (C.G), R01HL105631 ( NIH ) (Y.Z), 30970931 (NSFC) (T.T), KSCX2-YW-R-148 ( the Knowledge Innovation Program of Chinese Academy of Sciences ), 31100557 (NSFC) (H.Z), and the Chinese Academy of Sciences “One-Hundred-Talent Program” (C.G).

PY - 2013/5/1

Y1 - 2013/5/1

N2 - The Y-family of DNA polymerases support of translesion DNA synthesis (TLS) associated with stalled DNA replication by DNA damage. Recently, a number of studies suggest that some specialized TLS polymerases also support other aspects of DNA metabolism beyond TLS in vivo. Here we show that mouse polymerase kappa (Polκ) could accumulate at laser-induced sites of damage in vivo resembling polymerases eta and iota. The recruitment was mediated through Polκ C-terminus which contains the PCNA-interacting peptide, ubiquitin zinc finger motif 2 and nuclear localization signal. Interestingly, this recruitment was significantly reduced in MSH2-deficient LoVo cells and Rad18-depleted cells. We further observed that Polκ-deficient mouse embryo fibroblasts were abnormally sensitive to H2O2 treatment and displayed defects in both single-strand break repair and double-strand break repair. We speculate that Polκ may have an important role in strand break repair following oxidative stress in vivo.

AB - The Y-family of DNA polymerases support of translesion DNA synthesis (TLS) associated with stalled DNA replication by DNA damage. Recently, a number of studies suggest that some specialized TLS polymerases also support other aspects of DNA metabolism beyond TLS in vivo. Here we show that mouse polymerase kappa (Polκ) could accumulate at laser-induced sites of damage in vivo resembling polymerases eta and iota. The recruitment was mediated through Polκ C-terminus which contains the PCNA-interacting peptide, ubiquitin zinc finger motif 2 and nuclear localization signal. Interestingly, this recruitment was significantly reduced in MSH2-deficient LoVo cells and Rad18-depleted cells. We further observed that Polκ-deficient mouse embryo fibroblasts were abnormally sensitive to H2O2 treatment and displayed defects in both single-strand break repair and double-strand break repair. We speculate that Polκ may have an important role in strand break repair following oxidative stress in vivo.

KW - Laser micro-irradiation

KW - MSH2

KW - PCNA

KW - Polymerase kappa

KW - Strand break repair

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U2 - 10.1016/j.dnarep.2013.02.008

DO - 10.1016/j.dnarep.2013.02.008

M3 - Article

C2 - 23522793

AN - SCOPUS:84876724610

SN - 1568-7864

VL - 12

SP - 377

EP - 388

JO - DNA repair

JF - DNA repair

IS - 5

ER -

Mouse DNA polymerase kappa has a functional role in the repair of DNA strand breaks

Abstract

Keywords

ASJC Scopus subject areas

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