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PMID:11801590

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Citation

Gu, Y, Parker, A, Wilson, TM, Bai, H, Chang, DY and Lu, AL (2002) Human MutY homolog, a DNA glycosylase involved in base excision repair, physically and functionally interacts with mismatch repair proteins human MutS homolog 2/human MutS homolog 6. J. Biol. Chem. 277:11135-42

Abstract

Adenines mismatched with guanines or 7,8-dihydro-8-oxo-deoxyguanines that arise through DNA replication errors can be repaired by either base excision repair or mismatch repair. The human MutY homolog (hMYH), a DNA glycosylase, removes adenines from these mismatches. Human MutS homologs, hMSH2/hMSH6 (hMutSalpha), bind to the mismatches and initiate the repair on the daughter DNA strands. Human MYH is physically associated with hMSH2/hMSH6 via the hMSH6 subunit. The interaction of hMutSalpha and hMYH is not observed in several mismatch repair-defective cell lines. The hMutSalpha binding site is mapped to amino acid residues 232-254 of hMYH, a region conserved in the MutY family. Moreover, the binding and glycosylase activities of hMYH with an A/7,8-dihydro-8-oxo-deoxyguanine mismatch are enhanced by hMutSalpha. These results suggest that protein-protein interactions may be a means by which hMYH repair and mismatch repair cooperate in reducing replicative errors caused by oxidized bases.

Links

PubMed Online version:10.1074/jbc.M108618200

Keywords

Adenosine Triphosphatases; Amino Acid Sequence; Bacterial Proteins/metabolism; Base Sequence; DNA Glycosylases; DNA Primers; DNA Repair; DNA-Binding Proteins; Escherichia coli Proteins; Humans; Molecular Sequence Data; MutS DNA Mismatch-Binding Protein; N-Glycosyl Hydrolases/metabolism; Protein Isoforms/metabolism; Sequence Homology, Amino Acid

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:MSH6

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9UIF7

F

Seeded From UniProt

complete

HUMAN:MUTYH

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P52701

F

Seeded From UniProt

complete

HUMAN:MSH2

contributes_to

GO:0030983: mismatched DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:MSH2

contributes_to

GO:0032357: oxidized purine DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:MSH6

contributes_to

GO:0032357: oxidized purine DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:MSH6

contributes_to

GO:0030983: mismatched DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:MUTYH

NOT|enables

GO:0032405: MutLalpha complex binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:MUTYH

enables

GO:0032407: MutSalpha complex binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:MUTYH

NOT|enables

GO:0032406: MutLbeta complex binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:MUTYH

NOT|enables

GO:0032408: MutSbeta complex binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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