MutL: conducting the cell's response to mismatched and misaligned DNA.
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.
Polosina
Yaroslava Y
YY
Department of Biochemistry and Microbiology, University of Victoria, BC, Canada. polosina@uvic.ca
Cupples
Claire G
CG
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D045647:DNA Glycosylases / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism; D053843:DNA Mismatch Repair / Q000235:genetics / Q000502:physiology*; D004261:DNA Replication; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D000070956:MutL Proteins; D051719:MutS DNA Mismatch-Binding Protein / Q000378:metabolism; D011487:Protein Conformation; D015398:Signal Transduction; D027041:Somatic Hypermutation, Immunoglobulin
D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; C074770:MutL protein, E coli; C058093:UvrB protein, E coli; D000255:Adenosine Triphosphate; D004706:Endodeoxyribonucleases; C071421:vsr endonuclease; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase; D000251:Adenosine Triphosphatases; D000070956:MutL Proteins; D051719:MutS DNA Mismatch-Binding Protein; C497175:MutS protein, E coli; D004265:DNA Helicases