Evidence for the involvement of human DNA polymerase N in the repair of DNA interstrand cross-links

Laura Zietlow; Leigh Anne Smith; Mika Bessho; Tadayoshi Bessho

doi:10.1021/bi9015346

Evidence for the involvement of human DNA polymerase N in the repair of DNA interstrand cross-links

Laura Zietlow, Leigh Anne Smith, Mika Bessho, Tadayoshi Bessho

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44 Scopus citations

Abstract

Human DNA polymerase N (PolN) is an A-family nuclear DNA polymerase whose function is unknown. This study examines the possible role of PolN in DNA repair in human cells treated with PolN-targeted siRNA. HeLa cells with siRNA-mediated knockdown of PolN were more sensitive than control cells to DNA cross-linking agent mitomycin C (MMC) but were not hypersensitive to UV irradiation. The MMC hypersensitivity of PolN knockdown cells was rescued by the overexpression of DNA polymerase-proficient PolN but not by DNA polymerase-deficient PolN. Furthermore, in vitro experiments showed that purified PolN conducts low-efficiency nonmutagenic bypass of a psoralen DNA interstrand cross-link (ICL), whose structure resembles an intermediate in the proposed pathway of ICL repair. These results suggest that PolN might play a role in translesion DNA synthesis during ICL repair in human cells.

Original language	English (US)
Pages (from-to)	11817-11824
Number of pages	8
Journal	Biochemistry
Volume	48
Issue number	49
DOIs	https://doi.org/10.1021/bi9015346
State	Published - Dec 15 2009

ASJC Scopus subject areas

Biochemistry

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title = "Evidence for the involvement of human DNA polymerase N in the repair of DNA interstrand cross-links",

abstract = "Human DNA polymerase N (PolN) is an A-family nuclear DNA polymerase whose function is unknown. This study examines the possible role of PolN in DNA repair in human cells treated with PolN-targeted siRNA. HeLa cells with siRNA-mediated knockdown of PolN were more sensitive than control cells to DNA cross-linking agent mitomycin C (MMC) but were not hypersensitive to UV irradiation. The MMC hypersensitivity of PolN knockdown cells was rescued by the overexpression of DNA polymerase-proficient PolN but not by DNA polymerase-deficient PolN. Furthermore, in vitro experiments showed that purified PolN conducts low-efficiency nonmutagenic bypass of a psoralen DNA interstrand cross-link (ICL), whose structure resembles an intermediate in the proposed pathway of ICL repair. These results suggest that PolN might play a role in translesion DNA synthesis during ICL repair in human cells.",

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T1 - Evidence for the involvement of human DNA polymerase N in the repair of DNA interstrand cross-links

AU - Zietlow, Laura

AU - Smith, Leigh Anne

AU - Bessho, Mika

AU - Bessho, Tadayoshi

PY - 2009/12/15

Y1 - 2009/12/15

N2 - Human DNA polymerase N (PolN) is an A-family nuclear DNA polymerase whose function is unknown. This study examines the possible role of PolN in DNA repair in human cells treated with PolN-targeted siRNA. HeLa cells with siRNA-mediated knockdown of PolN were more sensitive than control cells to DNA cross-linking agent mitomycin C (MMC) but were not hypersensitive to UV irradiation. The MMC hypersensitivity of PolN knockdown cells was rescued by the overexpression of DNA polymerase-proficient PolN but not by DNA polymerase-deficient PolN. Furthermore, in vitro experiments showed that purified PolN conducts low-efficiency nonmutagenic bypass of a psoralen DNA interstrand cross-link (ICL), whose structure resembles an intermediate in the proposed pathway of ICL repair. These results suggest that PolN might play a role in translesion DNA synthesis during ICL repair in human cells.

AB - Human DNA polymerase N (PolN) is an A-family nuclear DNA polymerase whose function is unknown. This study examines the possible role of PolN in DNA repair in human cells treated with PolN-targeted siRNA. HeLa cells with siRNA-mediated knockdown of PolN were more sensitive than control cells to DNA cross-linking agent mitomycin C (MMC) but were not hypersensitive to UV irradiation. The MMC hypersensitivity of PolN knockdown cells was rescued by the overexpression of DNA polymerase-proficient PolN but not by DNA polymerase-deficient PolN. Furthermore, in vitro experiments showed that purified PolN conducts low-efficiency nonmutagenic bypass of a psoralen DNA interstrand cross-link (ICL), whose structure resembles an intermediate in the proposed pathway of ICL repair. These results suggest that PolN might play a role in translesion DNA synthesis during ICL repair in human cells.

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Evidence for the involvement of human DNA polymerase N in the repair of DNA interstrand cross-links

Abstract

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