Error-free and error-prone lesion bypass by human DNA polymerase kappa in vitro.

Abstract:

:Error-free lesion bypass and error-prone lesion bypass are important cellular responses to DNA damage during replication, both of which require a DNA polymerase (Pol). To identify lesion bypass DNA polymerases, we have purified human Polkappa encoded by the DINB1 gene and examined its response to damaged DNA templates. Here, we show that human Polkappa is a novel lesion bypass polymerase in vitro. Purified human Polkappa efficiently bypassed a template 8-oxoguanine, incorporating mainly A and less frequently C opposite the lesion. Human Polkappa most frequently incorporated A opposite a template abasic site. Efficient further extension required T as the next template base, and was mediated mainly by a one-nucleotide deletion mechanism. Human Polkappa was able to bypass an acetylaminofluorene-modified G in DNA, incorporating either C or T, and less efficiently A opposite the lesion. Furthermore, human Polkappa effectively bypassed a template (-)-trans-anti-benzo[a]pyrene-N:(2)-dG lesion in an error-free manner by incorporating a C opposite the bulky adduct. In contrast, human Polkappa was unable to bypass a template TT dimer or a TT (6-4) photoproduct, two of the major UV lesions. These results suggest that Polkappa plays an important role in both error-free and error-prone lesion bypass in humans.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Zhang Y,Yuan F,Wu X,Wang M,Rechkoblit O,Taylor JS,Geacintov NE,Wang Z

doi

10.1093/nar/28.21.4138

keywords:

subject

Has Abstract

pub_date

2000-11-01 00:00:00

pages

4138-46

issue

21

eissn

0305-1048

issn

1362-4962

journal_volume

28

pub_type

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