{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T13:43:19Z","timestamp":1783690999518,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:00:00Z","timestamp":1702425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["P20RR018759-08"],"award-info":[{"award-number":["P20RR018759-08"]}]},{"name":"National Institutes of Health","award":["DE030427"],"award-info":[{"award-number":["DE030427"]}]},{"name":"National Institutes of Health","award":["RSG-10-031-01-CCG"],"award-info":[{"award-number":["RSG-10-031-01-CCG"]}]},{"name":"American Cancer Society","award":["P20RR018759-08"],"award-info":[{"award-number":["P20RR018759-08"]}]},{"name":"American Cancer Society","award":["DE030427"],"award-info":[{"award-number":["DE030427"]}]},{"name":"American Cancer Society","award":["RSG-10-031-01-CCG"],"award-info":[{"award-number":["RSG-10-031-01-CCG"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Cells respond to DNA double-strand breaks by initiating DSB repair and ensuring a cell cycle checkpoint. The primary responder to DSB repair is non-homologous end joining, which is an error-prone repair pathway. However, when DSBs are generated after DNA replication in the G2 phase of the cell cycle, a second DSB repair pathway, homologous recombination, can come into action. Both ATM and ATR are important for DSB-induced DSB repair and checkpoint responses. One method of ATM and ATR working together is through the DNA end resection of DSBs. As a readout and marker of DNA end resection, RPA is phosphorylated at Ser4\/Ser8 of the N-terminus of RPA32 in response to DSBs. Here, the significance of RPA32 Ser4\/Ser8 phosphorylation in response to DNA damage, specifically in the S phase to G2 phase of the cell cycle, is examined. RPA32 Ser4\/Ser8 phosphorylation in G2 synchronized cells is necessary for increases in TopBP1 and Rad9 accumulation on chromatin and full activation of the ATR-dependent G2 checkpoint. In addition, our data suggest that RPA Ser4\/Ser8 phosphorylation modulates ATM-dependent KAP-1 phosphorylation and Rad51 chromatin loading in G2 cells. Through the phosphorylation of RPA Ser4\/Ser8, ATM acts as a partner with ATR in the G2 phase checkpoint response, regulating key downstream events including Rad9, TopBP1 phosphorylation and KAP-1 phosphorylation\/activation via the targeting of RPA32 Ser4\/Ser8.<\/jats:p>","DOI":"10.3390\/genes14122205","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T04:14:42Z","timestamp":1702440882000},"page":"2205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Role of RPA Phosphorylation in the ATR-Dependent G2 Cell Cycle Checkpoint"],"prefix":"10.3390","volume":"14","author":[{"given":"Shengqin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Oral Biology, University of Nebraska Medical Center College of Dentistry, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan M.","family":"Byrne","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, University of Nebraska Medical Center College of Dentistry, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas N.","family":"Byrne","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, University of Nebraska Medical Center College of Dentistry, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory G.","family":"Oakley","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, University of Nebraska Medical Center College of Dentistry, Lincoln, NE 68583, USA"},{"name":"Eppley Cancer Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5834","DOI":"10.1038\/sj.onc.1206682","article-title":"DNA damage checkpoint control in cells exposed to ionizing radiation","volume":"22","author":"Iliakis","year":"2003","journal-title":"Oncogene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.molcel.2010.09.019","article-title":"The DNA damage response: Making it safe to play with knives","volume":"40","author":"Ciccia","year":"2010","journal-title":"Mol. 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