Document Detail

Residues in the N-terminal domain of MutL required for mismatch repair in Bacillus subtilis.
MedLine Citation:
PMID:  22843852     Owner:  NLM     Status:  MEDLINE    
Mismatch repair is a highly conserved pathway responsible for correcting DNA polymerase errors incorporated during genome replication. MutL is a mismatch repair protein known to coordinate several steps in repair that ultimately results in strand removal following mismatch identification by MutS. MutL homologs from bacteria to humans contain well-conserved N-terminal and C-terminal domains. To understand the contribution of the MutL N-terminal domain to mismatch repair, we analyzed 14 different missense mutations in Bacillus subtilis MutL that were conserved with missense mutations identified in the human MutL homolog MLH1 from patients with hereditary nonpolyposis colorectal cancer (HNPCC). We characterized missense mutations in or near motifs important for ATP binding, ATPase activity, and DNA binding. We found that 13 of the 14 missense mutations conferred a substantial defect to mismatch repair in vivo, while three mutant alleles showed a dominant negative increase in mutation frequency to wild-type mutL. We performed immunoblot analysis to determine the relative stability of each mutant protein in vivo and found that, although most accumulated, several mutant proteins failed to maintain wild-type levels, suggesting defects in protein stability. The remaining missense mutations located in areas of the protein important for DNA binding, ATP binding, and ATPase activities of MutL compromised repair in vivo. Our results define functional residues in the N-terminal domain of B. subtilis MutL that are critical for mismatch repair in vivo.
Nicholas J Bolz; Justin S Lenhart; Steven C Weindorf; Lyle A Simmons
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-07-27
Journal Detail:
Title:  Journal of bacteriology     Volume:  194     ISSN:  1098-5530     ISO Abbreviation:  J. Bacteriol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-11     Completed Date:  2012-11-23     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  2985120R     Medline TA:  J Bacteriol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5361-7     Citation Subset:  IM    
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.
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MeSH Terms
Adenosine Triphosphatases / genetics,  metabolism*
Amino Acid Sequence
Bacillus subtilis / genetics*,  metabolism*
Bacterial Proteins / genetics,  metabolism*
Base Pair Mismatch / genetics*
DNA Mismatch Repair / physiology*
Gene Expression Regulation, Bacterial / physiology
Gene Expression Regulation, Enzymologic
Genomic Instability
Models, Molecular
Molecular Sequence Data
Protein Conformation
Reg. No./Substance:
0/Bacterial Proteins; EC 3.6.1.-/Adenosine Triphosphatases

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