Fine-structure analysis of activation-induced deaminase accessibility to class switch region R-loops

被引:50
作者
Yu, KF
Roy, D
Bayramyan, M
Haworth, IS
Lieber, MR
机构
[1] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA
[2] Univ So Calif, Keck Sch Med, Dept Mol Microbiol & Immunol, Los Angeles, CA 90033 USA
[3] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA
[4] Univ So Calif, Keck Sch Med, Dept Biol Sci, Los Angeles, CA 90033 USA
[5] Univ So Calif, Sch Pharm, Dept Pharmaceut Sci, Los Angeles, CA 90033 USA
关键词
D O I
10.1128/MCB.25.5.1730-1736.2005
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
Activation-induced deaminase (AID) is essential for class switch recombination and somatic hypermutation, and it has the ability to deaminate single-stranded DNA at cytidines. Mammalian class switch regions form R-loops upon transcription in the physiological orientation. The displaced DNA strand of an R-loop is forced to wrap around the RNA-DNA hybrid; hence, it may not have complete exposure to proteins. A fundamental question concerns the extent to which AID is accessible to the displaced strand of a transcription-generated R-loop. We used a minimal R-loop to carry out high-resolution analysis of the precise locations of AID action. We found that AID deaminates on the displaced DNA strand across the entire length of the R-loop. Displaced strand locations with a WRC (where W is A or T and R is A or G) sequence are preferred targets, but there are clear exceptions. These WRC deviations may be due to steric constraints on the accessibility of AID to these sites as the displaced strand twists around the RNA-DNA duplex. This phenomenon may explain the lack of WRC site preference at the mutations surrounding class switch recombination junctions.
引用
收藏
页码:1730 / 1736
页数:7
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