Aquarius is required for proper CtIP expression and homologous recombination repair View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Ryo Sakasai, Mayu Isono, Mitsuo Wakasugi, Mitsumasa Hashimoto, Yumi Sunatani, Tadashi Matsui, Atsushi Shibata, Tsukasa Matsunaga, Kuniyoshi Iwabuchi

ABSTRACT

Accumulating evidence indicates that transcription is closely related to DNA damage formation and that the loss of RNA biogenesis factors causes genome instability. However, whether such factors are involved in DNA damage responses remains unclear. We focus here on the RNA helicase Aquarius (AQR), a known R-loop processing factor, and show that its depletion in human cells results in the accumulation of DNA damage during S phase, mediated by R-loop formation. We investigated the involvement of Aquarius in DNA damage responses and found that AQR knockdown decreased DNA damage-induced foci formation of Rad51 and replication protein A, suggesting that Aquarius contributes to homologous recombination (HR)-mediated repair of DNA double-strand breaks (DSBs). Interestingly, the protein level of CtIP, a DSB processing factor, was decreased in AQR-knockdown cells. Exogenous expression of Aquarius partially restored CtIP protein level; however, CtIP overproduction did not rescue defective HR in AQR-knockdown cells. In accordance with these data, Aquarius depletion sensitized cells to genotoxic agents. We propose that Aquarius contributes to the maintenance of genomic stability via regulation of HR by CtIP-dependent and -independent pathways. More... »

PAGES

13808

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-017-13695-4

DOI

http://dx.doi.org/10.1038/s41598-017-13695-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1092262006

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29061988


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