Evidence for the involvement of human DNA polymerase N in the repair of DNA interstrand cross-links.
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.
Zietlow
Laura
L
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
LA
Bessho
Mika
M
Bessho
Tadayoshi
T
D001483:Base Sequence; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004249:DNA Damage / Q000235:genetics; D004265:DNA Helicases / Q000737:chemistry / Q000502:physiology; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000096:biosynthesis / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology
D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C095888:xeroderma pigmentosum group F protein; D016685:Mitomycin; D004259:DNA-Directed DNA Polymerase; C546205:POLN protein, human; D004265:DNA Helicases; D045643:DNA Repair Enzymes