Repair of dihydrouracil supported by base excision repair in mNTH1 knock-out cell extracts

被引：27

作者：

Elder, RH

Dianov, GL ^{[1
]}

机构：

[1] MRC, Radiat & Genome Stabil Unit, Harwell OX11 0RD, Oxon, England

[2] Christie Hosp NHS Trust, Paterson Inst Canc Res, Carcinogenesis Grp, Canc Res UK, Manchester M20 4BX, Lancs, England

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2002年 / 277卷 / 52期

关键词：

D O I：

10.1074/jbc.M208153200

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：

In mammalian cells, thymine glycols and other oxidized pyrimidines such as 5,6-dihydrouracil are removed from DNA by the NTH1 protein, a bifunctional DNA-N-glycosylase. However, mNTH1 knock-out mice in common with other DNA glycosylase-deficient mice do not show any severe abnormalities associated with accumulation of DNA damage and mutations. In the present study we used an in vitro repair system to investigate the mechanism for the removal of 5,6-dihydrouracil from DNA by mNTH1-deficient cell-free extracts derived from testes of mNTH1 knock-out mice. We found that these extracts are able to support the removal of 5,6-dihydrouracil from DNA at about 20% of the efficiency of normal extracts. Furthermore, we also found that Single-nucleotide patch base excision repair is the major pathway for removal of 5,6-dihydrouracil in mNTH1-deficient cell extracts, suggesting the involvement of other DNA glycosylase(s) in the removal of oxidized pyrimidines.

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页码：50487 / 50490

页数：4

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