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Strand-Biased Spreading of Mutations during Somatic Hypermutation
Shyam Unniraman and David G. Schatz
New Series, Vol. 317, No. 5842 (Aug. 31, 2007), pp. 1227-1230
Published by: American Association for the Advancement of Science
Stable URL: http://www.jstor.org/stable/20037708
Page Count: 4
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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.
Science © 2007 American Association for the Advancement of Science