Journal
SCIENCE
Volume 317, Issue 5842, Pages 1227-1230Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1145065
Keywords
-
Categories
Ask authors/readers for more resources
Somatic hypermutation ( SHM) is a major means by which diversity is achieved in antibody genes, and it is initiated by the deamination of cytosines to uracils in DNA by activation-induced deaminase ( AID). However, the process that leads from these initiating deamination events to mutations at other residues remains poorly understood. We demonstrate that a single cytosine on the top ( nontemplate) strand is sufficient to recruit AID and lead to mutations of upstream and downstream A/T residues. In contrast, the targeting of cytosines on the bottom strand by AID does not lead to substantial mutation of neighboring residues. This strand asymmetry is eliminated in mice deficient in mismatch repair, indicating that the error-prone mismatch repair machinery preferentially targets top-strand uracils in a way that promotes SHM during the antibody response.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available