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RPA complexes in Caenorhabditis elegans meiosis; unique roles in replication, meiotic recombination and apoptosis
Journal article   Open access   Peer reviewed

RPA complexes in Caenorhabditis elegans meiosis; unique roles in replication, meiotic recombination and apoptosis

Adam Hefel, Masayoshi Honda, Nicholas Cronin, Kailey Harrell, Pooja Patel, Maria Spies and Sarit Smolikove
Nucleic acids research, Vol.49(4), pp.2005-2026
02/26/2021
DOI: 10.1093/nar/gkaa1293
PMCID: PMC7913698
PMID: 33476370
url
https://doi.org/10.1093/nar/gkaa1293View
Published (Version of record) Open Access

Abstract

Replication Protein A (RPA) is a critical complex that acts in replication and promotes homologous recombination by allowing recombinase recruitment to processed DSB ends. Most organisms possess three RPA subunits (RPA1, RPA2, RPA3) that form a trimeric complex critical for viability. The Caenorhabditis elegans genome encodes RPA-1, RPA-2 and an RPA-2 paralog RPA-4. In our analysis, we determined that RPA-2 is critical for germline replication and normal repair of meiotic DSBs. Interestingly, RPA-1 but not RPA-2 is essential for somatic replication, in contrast to other organisms that require both subunits. Six different hetero- and homodimeric complexes containing permutations of RPA-1, RPA-2 and RPA-4 can be detected in whole animal extracts. Our in vivo studies indicate that RPA-1/4 dimer is less abundant in the nucleus and its formation is inhibited by RPA-2. While RPA-4 does not participate in replication or recombination, we find that RPA-4 inhibits RAD-51 filament formation and promotes apoptosis of a subset of damaged nuclei. Altogether these findings point to sub-functionalization and antagonistic roles of RPA complexes in C. elegans.
Apoptosis DNA Replication Animals Caenorhabditis elegans - genetics Caenorhabditis elegans Proteins - analysis Caenorhabditis elegans Proteins - metabolism Caenorhabditis elegans Proteins - physiology DNA Breaks, Double-Stranded Meiosis - genetics Mitosis - genetics Rad51 Recombinase - analysis Recombination, Genetic Replication Protein A - metabolism Replication Protein A - physiology

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