Evidence for the Involvement of Human DNA Polymerase N in the Repair of DNA Interstrand Cross-Links

被引：41

作者：

Zietlow, Laura ^{[1
]}

Smith, Leigh Anne ^{[1
]}

Bessho, Mika ^{[1
]}

Bessho, Tadayoshi ^{[1
]}

机构：

[1] Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA

来源：

BIOCHEMISTRY | 2009年 / 48卷 / 49期

基金：

美国国家卫生研究院;

关键词：

NUCLEOTIDE EXCISION-REPAIR; TRANSLESION SYNTHESIS; IN-VITRO; THYMINE GLYCOLS; MAMMALIAN-CELLS; FANCONI-ANEMIA; THETA POLQ; BYPASS; REPLICATION; DAMAGE;

D O I：

10.1021/bi9015346

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Human DNA polymerise 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 polymerise-proficient PolN but not by DNA polymerise-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.

引用

页码：11817 / 11824

页数：8

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