Document Detail

Mismatch repair in Escherichia coli enhances instability of (CTG)n triplet repeats from human hereditary diseases.
MedLine Citation:
PMID:  7479928     Owner:  NLM     Status:  MEDLINE    
Long CTG triplet repeats which are associated with several human hereditary neuromuscular disease genes are stabilized in ColE1-derived plasmids in Escherichia coli containing mutations in the methyl-directed mismatch repair genes (mutS, mutL, or mutH). When plasmids containing (CTG)180 were grown for about 100 generations in mutS, mutL, or mutH strains, 60-85% of the plasmids contained a full-length repeat, whereas in the parent strain only about 20% of the plasmids contained the full-length repeat. The deletions occur only in the (CTG)180 insert, not in DNA flanking the repeat. While many products of the deletions are heterogeneous in length, preferential deletion products of about 140, 100, 60, and 20 repeats were observed. We propose that the E. coli mismatch repair proteins recognize three-base loops formed during replication and then generate long single-stranded gaps where stable hairpin structures may form which can be bypassed by DNA polymerase during the resynthesis of duplex DNA. Similar studies were conducted with plasmids containing CGG repeats; no stabilization of these triplets was found in the mismatch repair mutants. Since prokaryotic and human mismatch repair proteins are similar, and since several carcinoma cell lines which are defective in mismatch repair show instability of simple DNA microsatellites, these mechanistic investigations in a bacterial cell may provide insights into the molecular basis for some human genetic diseases.
A Jaworski; W A Rosche; R Gellibolian; S Kang; M Shimizu; R P Bowater; R R Sinden; R D Wells
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  92     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1995 Nov 
Date Detail:
Created Date:  1995-12-28     Completed Date:  1995-12-28     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  11019-23     Citation Subset:  IM    
Center for Genome Research, Texas A&M University, Texas Medical Center, Houston 77030-3303, USA.
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MeSH Terms
Adenosine Triphosphatases*
Bacterial Proteins / physiology
DNA Repair*
DNA Repair Enzymes*
DNA Replication
DNA, Bacterial / biosynthesis
DNA-Binding Proteins / physiology
Endodeoxyribonucleases / physiology
Escherichia coli / genetics*
Escherichia coli Proteins*
MutS DNA Mismatch-Binding Protein
Rec A Recombinases / metabolism
Sequence Deletion
Trinucleotide Repeats*
Grant Support
Reg. No./Substance:
0/Bacterial Proteins; 0/DNA, Bacterial; 0/DNA-Binding Proteins; 0/Escherichia coli Proteins; 0/MutL protein, E coli; EC 2.7.7.-/Rec A Recombinases; EC 3.1.-/Endodeoxyribonucleases; EC 3.1.21.-/methyl-directed mismatch repair protein, E coli; EC 3.6.1.-/Adenosine Triphosphatases; EC DNA Mismatch-Binding Protein; EC protein, E coli; EC 6.5.1.-/DNA Repair Enzymes

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