Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells.
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.
Drummond
J T
JT
Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
Li
G M
GM
Longley
M J
MJ
Modrich
P
P
D000595:Amino Acid Sequence; D001482:Base Composition; D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000302:isolation & purification* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009154:Mutation; D009692:Nucleic Acid Heteroduplexes / Q000378:metabolism; D017384:Sequence Deletion; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D009692:Nucleic Acid Heteroduplexes