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PMID: 19908865 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Biochemistry ·Vol. 48 ·No. 49 ·2009-12-15 ·Pages 11817-24

Zietlow L, Smith LA, Bessho M, Bessho T

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.

MeSH Terms
Base Sequence Cell Nucleus/drug effects,enzymology,genetics Cross-Linking Reagents/pharmacology DNA Damage/genetics DNA Helicases/chemistry,physiology DNA Repair/drug effects,genetics DNA Repair Enzymes/chemistry,physiology DNA-Binding Proteins/genetics DNA-Directed DNA Polymerase/biosynthesis,chemistry,deficiency,genetics,physiology HeLa Cells Humans Mitomycin/pharmacology Molecular Sequence Data Nuclear Proteins/biosynthesis,deficiency,genetics,physiology RNA, Small Interfering/pharmacology
Chemicals
Cross-Linking Reagents DNA-Binding Proteins Nuclear Proteins RNA, Small Interfering xeroderma pigmentosum group F protein Mitomycin DNA-Directed DNA Polymerase POLN protein, human DNA Helicases DNA Repair Enzymes
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Zietlow Laura
The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
Smith Leigh Anne
Bessho Mika
Bessho Tadayoshi
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Article Info
Journal
Biochemistry
Abbr.
Biochemistry
ISSN
1520-4995
DOI
10.1021/bi9015346
Published
2009-12-15
Pages
11817-24
Language
English
Region
United States
NLM ID
0370623
PMCID
PMC2790558
Subset
IM
Grants
NCI NIH HHS · 5T32 CA09476 · United States
NCI NIH HHS · R01 CA95291 · United States
NCRR NIH HHS · P20 RR016469 · United States
NCI NIH HHS · P30 CA036727 · United States
NCI NIH HHS · T32 CA009476 · United States
NCI NIH HHS · P30CA036727 · United States
NCI NIH HHS · R01 CA095291-05 · United States
NIGMS NIH HHS · R01 GM080458-02 · United States
NCI NIH HHS · R01 CA095291 · United States
NIGMS NIH HHS · R01 GM080458 · United States
External Links
PubMed source DOI: 10.1021/bi9015346 PMC Full Text View journal details
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