Crystal structures of mismatch repair protein MutS and its complex with a substrate DNA.

Abstract:

:DNA mismatch repair is critical for increasing replication fidelity in organisms ranging from bacteria to humans. MutS protein, a member of the ABC ATPase superfamily, recognizes mispaired and unpaired bases in duplex DNA and initiates mismatch repair. Mutations in human MutS genes cause a predisposition to hereditary nonpolyposis colorectal cancer as well as sporadic tumours. Here we report the crystal structures of a MutS protein and a complex of MutS with a heteroduplex DNA containing an unpaired base. The structures reveal the general architecture of members of the MutS family, an induced-fit mechanism of recognition between four domains of a MutS dimer and a heteroduplex kinked at the mismatch, a composite ATPase active site composed of residues from both MutS subunits, and a transmitter region connecting the mismatch-binding and ATPase domains. The crystal structures also provide a molecular framework for understanding hereditary nonpolyposis colorectal cancer mutations and for postulating testable roles of MutS.

journal_name

Nature

journal_title

Nature

authors

Obmolova G,Ban C,Hsieh P,Yang W

doi

10.1038/35037509

keywords:

subject

Has Abstract

pub_date

2000-10-12 00:00:00

pages

703-10

issue

6805

eissn

0028-0836

issn

1476-4687

journal_volume

407

pub_type

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