Replication protein-A, RPA, plays a pivotal role in the maintenance of recombination checkpoint in yeast meiosis

Abstract

SummaryDNA double-strand breaks (DSBs) activate DNA damage responses (DDR) in both mitotic and meiotic cells. Meiotic DSBs induce homologous recombination monitored by a meiotic DDR called the recombination checkpoint for the pachytene exit in meiotic prophase I. In this study, we showed the essential role of a single-stranded DNA (ssDNA) binding protein, Replication protein-A (RPA), in the maintenance of the recombination checkpoint duringS. cerevisiaemeiosis. The depletion of an RPA subunit, Rfa1, in a recombination-defectivedmc1mutant, fully alleviates the pachytene arrest with the persistent unrepaired DSBs. RPA depletion downregulates a meiosis-specific CHK2 homolog, Mek1, which in turn activates Ndt80 transcriptional activator for pachytene exit. These support the idea that RPA is a sensor of ssDNAs for the activation of meiotic DDR. Rfa1 depletion also accelerates the prophase I delay induced by thezip1mutant defective in both chromosome synapsis and the recombination, suggesting that the accumulation of ssDNAs rather than defective synapsis triggers prophase I relay in thezip1mutant.