Previously, we reported evidence suggesting that Saccharomyces cerevisiae MutLα, composed of Mlh1p and Pms1p, was a functional member of the gyrase b/Hsp90/MutL (GHL) dimeric ATPase superfamily characterized by highly conserved ATPase domains. Similar to other GHL ATPases, these putative ATPase domains of MutLα may be important for the recruitment and/or activation of downstream effectors. One downstream effector candidate is Exo1p, a 5′-3′ double stranded DNA exonuclease that has previously been implicated in DNA mismatch repair (MMR). Here we report yeast two-hybrid results suggesting that Exo1p can interact physically with MutLα through the Mlh1p subunit. We also report epistasis analysis involving MutLα ATPase mutations combined with exo1Δ. One interpretation of our genetic results is that MutLα ATPase domains function to direct Exo1p and other functionally redundant exonucleases during MMR. Finally, our results show that much of the increase in spontaneous mutation observed in an exo1Δ strain is REV3-dependent, in turn suggesting that Exo1p is also involved in one or more MMR-independent mutation avoidance pathways.
|Original language||English (US)|
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Aug 14 2001|
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