Nucleic Acids Research, Vol 24, Issue 13 2498-2504, Copyright © 1996 by Oxford University Press
A Aronshtam and MG Marinus
The mutL gene product is part of the dam-directed mismatch repair system of
Escherichia coli but has no known enzymatic function. It forms a complex on
heteroduplex DNA with the mismatch recognition MutS protein and with MutH,
which has latent endonuclease activity. An N- terminal hexahistidine-tagged
MutL was constructed which was active in vivo. As a first stop to determine
the functional domains of MutL, we have isolated 72 hydroxylamine-induced
plasmid-borne mutations which impart a dominant-negative phenotype to the
wild-type strain for increased spontaneous mutagenesis. None of the
mutations complement a mutL deletion mutant, indicating that the mutant
proteins by themselves are inactive. All the dominant mutations but one
could be complemented by the wild-type mutL at about the same gene dosage.
DNA sequencing indicated that the mutations affected 22 amino acid residues
located between positions 16 and 549 of the 615 amino acid protein. In the
N- terminal half of the protein, 12 out of 15 amino acid replacements occur
at positions conserved in various eukaryotic MutL homologs. All but one of
the sequence changes affecting the C-terminal end of the protein are
nonsense mutations.
ARTICLES
Dominant negative mutator mutations in the mutL gene of Escherichia coli
Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
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