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

Abstract:

: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.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Nilsen H,Rosewell I,Robins P,Skjelbred CF,Andersen S,Slupphaug G,Daly G,Krokan HE,Lindahl T,Barnes DE

doi

10.1016/s1097-2765(00)80271-3

subject

Has Abstract

pub_date

2000-06-01 00:00:00

pages

1059-65

issue

6

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(00)80271-3

journal_volume

5

pub_type

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