Genome-Wide Somatic Hypermutation

DNA mutagenesis is generally considered harmful. Yet activated B cells normally mutate the Ig loci. Because this somatic hypermutation is potentially dangerous, it has been hypothesized that mutations do not occur throughout the genome but instead are actively targeted to the Ig loci. Here we challe...

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Bibliographic Details
Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 101; no. 19; pp. 7352 - 7356
Main Authors:	Wang, Clifford L., Harper, Ryan A., Wabl, Matthias, Weigert, Martin G.
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 11-05-2004 National Acad Sciences
Subjects:	AIDS B lymphocytes Biological Sciences Cell cycle Cell Line Cell lines Cultured cells Deoxyribonucleic acid DNA Genes, Reporter Genetic loci Genetic mutation Genetics Genome Genomes Immunoglobulin constant regions Journalism Mutation Reporter genes
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Summary:	DNA mutagenesis is generally considered harmful. Yet activated B cells normally mutate the Ig loci. Because this somatic hypermutation is potentially dangerous, it has been hypothesized that mutations do not occur throughout the genome but instead are actively targeted to the Ig loci. Here we challenge this longstanding and widely accepted hypothesis. We demonstrate that hypermutation requires no Ig gene sequences. Instead, activation-induced cytidine deaminase and other trans-acting hypermutation factors may function as general mutators.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 Abbreviations: AID, activation-induced cytidine deaminase; V, variable; YFP, yellow fluorescent protein. To whom correspondence should be addressed. E-mail: cliffw@itsa.ucsf.edu. Communicated by Martin G. Weigert, Princeton University, Princeton, NJ, March 23, 2004
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.0402009101