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MutL: conducting the cell's response to mismatched and misaligned DNA
Author(s) -
Polosina Yaroslava Y.,
Cupples Claire G.
Publication year - 2010
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.200900089
Subject(s) - dna mismatch repair , effector , biology , dna repair , dna , microbiology and biotechnology , dna damage , dna replication , nucleotide excision repair , base excision repair , base pair , somatic hypermutation , genetics , b cell , antibody
Base pair mismatches in DNA arise from errors in DNA replication, recombination, and biochemical modification of bases. Mismatches are inherently transient. They are resolved passively by DNA replication, or actively by enzymatic removal and resynthesis of one of the bases. The first step in removal is recognition of strand discontinuity by one of the MutS proteins. Mismatches arising from errors in DNA replication are repaired in favor of the base on the template strand, but other mismatches trigger base excision or nucleotide excision repair (NER), or non‐repair pathways such as hypermutation, cell cycle arrest, or apoptosis. We argue that MutL homologues play a key role in determining biologic outcome by recruiting and/or activating effector proteins in response to lesion recognition by MutS. We suggest that the process is regulated by conformational changes in MutL caused by cycles of ATP binding and hydrolysis, and by physiologic changes which influence effector availability.