Binding of mismatched microsatellite DNA sequences by the human MSH2 protein.
Alteration of the human mismatch repair gene hMSH2 has been linked to the microsatellite DNA instability found in hereditary nonpolyposis colon cancer and several sporadic cancers. This microsatellite DNA instability is thought to arise from defective repair of DNA replication errors that create insertion-deletion loop-type (IDL) mismatched nucleotides. Here, it is shown that purified hMSH2 protein efficiently and specifically binds DNA containing IDL mismatches of up to 14 nucleotides. These results support a direct role for hMSH2 in mutation avoidance and microsatellite stability in human cells.
Fishel
R
R
Department of Microbiology and Molecular Genetics, Markey Center for Molecular Genetics, University of Vermont School of Medicine, Burlington 05405.
Ewel
A
A
Lee
S
S
Lescoe
M K
MK
Griffith
J
J
D001482:Base Composition; D001483:Base Sequence; D004260:DNA Repair; D004276:DNA, Satellite / Q000378:metabolism*; D004268:DNA-Binding Proteins; D006801:Humans; D008969:Molecular Sequence Data; D051718:MutS Homolog 2 Protein; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*
D004276:DNA, Satellite; D004268:DNA-Binding Proteins; D009692:Nucleic Acid Heteroduplexes; D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein