期刊
NUCLEIC ACIDS RESEARCH
卷 37, 期 10, 页码 3431-3441出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkp201
关键词
-
资金
- NCI NIH HHS [R01 CA085344] Funding Source: Medline
DNA polymerase (Pol ) is a key enzyme in DNA base excision repair, and an important factor for maintaining genome integrity and stability. More than 30% of human tumors characterized to date express DNA Pol variants, many of which result from a single nucleotide residue substitution. However, in most cases, their precise functional deficiency and relationship to cancer susceptibility are still unknown. In the current work, we show that a polymorphism encoding an arginine to glutamine substitution, R137Q, has lower polymerase activity. The substitution also affects the interaction between Pol and proliferating cell nuclear antigen (PCNA). These defects impair the DNA repair capacity of Pol in reconstitution assays, as well as in cellular extracts. Expression of wild-type Pol in pol (/) mouse embryonic fibroblast (MEF) cells restored cellular resistance to DNA damaging reagents such as methyl methanesulfonate (MMS) and N-methyl-N-nitrosourea (MNU), while expression of R137Q in pol (/) MEF cells failed to do so. These data indicate that polymorphisms in base excision repair genes may contribute to the onset and development of cancers.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据