Requirement of mammalian DNA polymerase-beta in base-excision repair

被引：757

作者：

Sobol, RW ^{[1
]}

Horton, JK ^{[1
]}

Kuhn, R ^{[1
]}

Gu, H ^{[1
]}

Singhal, RK ^{[1
]}

Prasad, R ^{[1
]}

Rajewsky, K ^{[1
]}

Wilson, SH ^{[1
]}

机构：

[1] UNIV COLOGNE,INST GENET,D-50931 COLOGNE,GERMANY

来源：

NATURE | 1996年 / 379卷 / 6561期

关键词：

D O I：

10.1038/379183a0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

SYNTHESIS Of DNA by DNA polymerase-beta is distributive on single-stranded DNA templates, but short DNA gaps with a 5' PO4 in the gap are filled processively to completion(1,2). In vitro studies have suggested a role of beta-polymerase in different types of DNA repair(3-9). However, the significance of these studies to the in vivo role of beta-polymerase has remained unclear. Because genetic studies are essential for determining the physiological role of a gene, we established embryonic fibroblast cell lines homozygous for a deletion mutation in the gene encoding DNA polymerase-beta. Extracts from these cell lines were found to be defective in uracil-initiated base-excision repair. The beta-polymerase-deleted cells are normal in viability and growth characteristics, although they exhibit increased sensitivity to monofunctional DNA-alkylating agents, but not to other DNA-damaging agents. Both the deficiency in base-excision repair and hypersensitivity to DNA-alkylating agents are rescued following stable transfection with a wild-type beta-polymerase minitransgene. These studies demonstrate that beta-polymerase functions specifically in base-excision repair in vivo.

引用

页码：183 / 186

页数：4

共 17 条

[1] PREPARING NUCLEI FROM CELLS IN MONOLAYER-CULTURES SUITABLE FOR COUNTING AND FOR FOLLOWING SYNCHRONIZED CELLS THROUGH THE CELL-CYCLE [J].