RPA mediates recombination repair during replication stress and is displaced from DNA by checkpoint signalling in human cells.

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The replication protein A (RPA) is involved in most, if not all, nuclear metabolism involving single-stranded DNA. Here, we show that RPA is involved in genome maintenance at stalled replication forks by the homologous recombination repair system in humans. Depletion of the RPA protein inhibited the formation of RAD51 nuclear foci after hydroxyurea-induced replication stalling leading to persistent unrepaired DNA double-strand breaks (DSBs). We demonstrate a direct role of RPA in homology directed recombination repair. We find that RPA is dispensable for checkpoint kinase 1 (Chk1) activation and that RPA directly binds RAD52 upon replication stress, suggesting a direct role in recombination repair. In addition we show that inhibition of Chk1 with UCN-01 decreases dissociation of RPA from the chromatin and inhibits association of RAD51 and RAD52 with DNA. Altogether, our data suggest a direct role of RPA in homologous recombination in assembly of the RAD51 and RAD52 proteins. Furthermore, our data suggest that replacement of RPA with the RAD51 and RAD52 proteins is affected by checkpoint signalling.
Original languageEnglish
JournalJournal of Molecular Biology
Volume373
Issue number1
Pages (from-to)38-47
Number of pages9
ISSN0022-2836
DOIs
Publication statusPublished - 2007

Bibliographical note

Keywords: Cell Line, Tumor; DNA Damage; DNA Repair; DNA Replication; Enzyme Activation; Genes, cdc; Humans; Hydroxyurea; Nucleic Acid Synthesis Inhibitors; Protein Kinases; Rad51 Recombinase; Rad52 DNA Repair and Recombination Protein; Replication Protein A; Signal Transduction

ID: 5015607