Uracil-DNA glycosylase (UNG)-deficient mice reveal a primary role of the enzyme during DNA replication

被引：271

作者：

Nilsen, H

Rosewell, I

Robins, P

Skjelbred, CF

Andersen, S

Slupphaug, G

Daly, G

Krokan, HE

Lindahl, T

Barnes, DE

机构：

[1] Imperial Canc Res Fund, Clare Hall Labs, S Mimms EN6 3LD, Herts, England

[2] Norwegian Univ Sci & Technol, Inst Canc Res & Mol Biol, N-7005 Trondheim, Norway

来源：

MOLECULAR CELL | 2000年 / 5卷 / 06期

关键词：

D O I：

10.1016/S1097-2765(00)80271-3

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：

Gene-targeted knockout mice have been generated lacking the major uracil-DNA glycosylase, UNG. In contrast to ung(-) mutants of bacteria and yeast, such mice do not exhibit a greatly increased spontaneous mutation frequency. However, there is only slow removal of uracil from misincorporated dUMP in isolated ung(-/-) nuclei and an elevated steady-state level of uracil in DNA in dividing ung(-/-) cells. A backup uracil-excising activity in tissue extracts from ung null mice, with properties indistinguishable from the mammalian SMUG1 DNA glycosylase, may account for the repair of premutagenic U:G mispairs resulting from cytosine deamination in vivo. The nuclear UNG protein has apparently evolved a specialized role in mammalian cells counteracting U:A base pairs formed by use of dUTP during DNA synthesis.

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页码：1059 / 1065

页数：7

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