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Science 20 February 1998:
Vol. 279. no. 5354, pp. 1207 - 1210
DOI: 10.1126/science.279.5354.1207
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Reports

Mismatch Repair Co-opted by Hypermutation

Marilia Cascalho, Jamie Wong, Charles Steinberg, Matthias Wabl *

Mice homozygous for a disrupted allele of the mismatch repair gene Pms2 have a mutator phenotype. When this allele is crossed into quasi-monoclonal (QM) mice, which have a very limited B cell repertoire, homozygotes have fewer somatic mutations at the immunoglobulin heavy chain and lambda  chain loci than do heterozygotes or wild-type QM mice. That is, mismatch repair seems to contribute to somatic hypermutation rather than stifling it. It is suggested that at immunoglobulin loci in hypermutable B cells, mismatched base pairs are "corrected" according to the newly synthesized DNA strand, thereby fixing incipient mutations instead of eliminating them.

Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-0670, USA.
*   To whom correspondence should be addressed. E-mail: mutator{at}itsa.ucsf.edu

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