Science, Vol 268, Issue 5219, 1909-1912
Copyright © 1995 by American Association for the Advancement of Science
Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells
JT Drummond,
GM Li,
MJ Longley,
and
P Modrich
Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
A mismatch-binding heterodimer of hMSH2 and a 160-kilodalton polypeptide has been isolated from HeLa cells by virtue of its ability to restore mismatch repair to nuclear extracts of hMSH2-deficient LoVo colorectal tumor cells. This heterodimer, designated hMutS alpha, also restores mismatch repair to extracts of alkylation-tolerant MT1 lymphoblastoid cells and HCT-15 colorectal tumor cells, which are selectively defective in the repair of base-base and single-nucleotide insertion-deletion mismatches. Because HOT-15 cells appear to be free of hMSH2 mutations, this selective repair defect is likely a result of a deficiency of the hMutS alpha 160-kilodalton subunit, and mutations in the corresponding gene may confer hypermutability and cancer predisposition.
