Positive and negative regulators of RAD51/DMC1 in homologous recombination and DNA replication

Abstract

RAD51 recombinase plays a central role in homologous recombination (HR) by forming a nucleoprotein filament on single-stranded DNA (ssDNA) to catalyze homology search and strand exchange between the ssDNA and a homologous double-stranded DNA (dsDNA). The catalytic activity of RAD51 assembled on ssDNA is critical for the DNA-homology-mediated repair of DNA double-strand breaks in somatic and meiotic cells and restarting stalled replication forks during DNA replication. The RAD51-ssDNA complex also plays a structural role in protecting the regressed/reversed replication fork. Two types of regulators control RAD51 filament formation, stability, and dynamics, namely positive regulators, including mediators, and negative regulators, so-called remodelers. The appropriate balance of action by the two regulators assures genome stability. This review describes the roles of positive and negative RAD51 regulators in HR and DNA replication and its meiosis-specific homolog DMC1 in meiotic recombination. We also provide future study directions for a comprehensive understanding of RAD51/DMC1-mediated regulation in maintaining and inheriting genome integrity.

Keywords: DNA repair; DNA replication; Homologous recombination; Mediator; Meiotic recombination; RAD51; Remodeler.