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

• Published in: Scientific reports Vol. 14; no. 1; p. 9550
• Main Authors: Sampathkumar, Arivarasan, Zhong, Chen, Tang, Yuting, Fujita, Yurika, Ito, Masaru, Shinohara, Akira
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.04.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/337/1427; 631/337/149; 631/80/641/1633; 631/80/641/2187; Auxin degron; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Chromosomes; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA Breaks, Double-Stranded; DNA damage; DNA, Single-Stranded - genetics; DNA, Single-Stranded - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Homologous Recombination; Humanities and Social Sciences; Kinases; MAP Kinase Kinase 1 - genetics; MAP Kinase Kinase 1 - metabolism; Meiosis; MEK1 kinase; multidisciplinary; Mutants; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Pachytene; Prophase; Proteins; Recombination checkpoint; Recombination, Genetic; Replication; Replication Protein A - genetics; Replication Protein A - metabolism; Rfa1; RPA; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Science; Science (multidisciplinary); Single-stranded DNA; Transcription Factors; Yeast; Yeasts; Recombination checkpoint; RPA; Rfa1; Homologous recombination; Meiosis; Auxin degron; Synapsis checkpoint
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-60082-x

DNA double-strand breaks (DSBs) activate DNA damage responses (DDRs) in both mitotic and meiotic cells. A single-stranded DNA (ssDNA) binding protein, Replication protein-A (RPA) binds to the ssDNA formed at DSBs to activate ATR/Mec1 kinase for the response. Meiotic DSBs induce homologous recombination monitored by a meiotic DDR called the recombination checkpoint that blocks the pachytene exit in meiotic prophase I. In this study, we further characterized the essential role of RPA in the maintenance of the recombination checkpoint during Saccharomyces cerevisiae meiosis. The depletion of an RPA subunit, Rfa1, in a recombination-defective dmc1 mutant, fully alleviates the pachytene arrest with the persistent unrepaired DSBs. RPA depletion decreases the activity of a meiosis-specific CHK2 homolog, Mek1 kinase, which in turn activates the Ndt80 transcriptional regulator 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 in the zip1 mutant defective in both chromosome synapsis and the recombination, consistent with the notion that the accumulation of ssDNAs rather than defective synapsis triggers prophase I delay in the zip1 mutant.