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Publication : Strand-biased spreading of mutations during somatic hypermutation.

First Author  Unniraman S Year  2007
Journal  Science Volume  317
Issue  5842 Pages  1227-30
PubMed ID  17761884 Mgi Jnum  J:139793
Mgi Id  MGI:3810173 Doi  10.1126/science.1145065
Citation  Unniraman S, et al. (2007) Strand-biased spreading of mutations during somatic hypermutation. Science 317(5842):1227-30
abstractText  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.
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