Evidence that the DNA Mismatch Repair System Removes 1-nt Okazaki Fragment Flaps [Molecular Bases of Disease]

July 29th, 2015 by Kadyrova, L. Y., Dahal, B. K., Kadyrov, F. A.

The MMR system plays a major role in promoting genome stability and suppressing carcinogenesis. In this work, we investigated whether the MMR system is involved in Okazaki fragment maturation. We found that in the yeast Saccharomyces cerevisiae the MMR system and the flap endonuclease Rad27 act in overlapping pathways that protect the nuclear genome from 1-bp insertions. In addition, we determined that purified yeast and human MutSα proteins recognize 1-nt DNA and RNA flaps. In reconstituted human systems, MutSα, PCNA, and RFC activate MutLα endonuclease to remove the flaps. ATPase and endonuclease mutants of MutLα are defective in the flap removal. These results suggest that the MMR system contributes to the removal of 1-nt Okazaki fragment flaps.