{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:20:51Z","timestamp":1791519651555,"version":"4.3.4"},"reference-count":72,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,12,14]],"date-time":"2009-12-14T00:00:00Z","timestamp":1260748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cytometry Pt A"],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>It has been reported that exposure to UV light triggers DNA damage response (DDR) seen as induction of \u03b3H2AX not only in S\u2010 but also in G<jats:sub>1<\/jats:sub>\u2010phase cells. In the present study, in addition to \u03b3H2AX, we assessed other markers of DDR, namely phosphorylation of ATM on <jats:italic>Ser<\/jats:italic>1981, of ATM\/ATR substrate on Ser\/Thr at SQ\/TQ cluster domains and of the tumor suppressor p53 on <jats:italic>Ser<\/jats:italic>15, in human pulmonary carcinoma A549 cells irradiated with 50 J\/m<jats:sup>2<\/jats:sup> of UV\u2010B. Phosphorylation of these proteins detected with phospho\u2010specific Abs and measured by laser scanning cytometry in relation the cell cycle phase was found to be selective to S\u2010phase cells. The kinetics of phosphorylation of ATM was strikingly similar to that of ATM\/ATR substrate, peaking at 30 min after UV irradiation and followed by rapid dephosphorylation. The peak of H2AX phosphorylation was seen at 2 h and the peak of p53 phosphorylation at 4 h after exposure to UV light. Local high spatial density of these phospho\u2010proteins reported by intensity of maximal pixel of immunofluorescence in the DDR nuclear foci was distinctly more pronounced in the early compared to late portion of S\u2010phase. Exposure of cells to UV following 1 h pulse\u2010labeling of their DNA with 5\u2010ethynyl\u20102\u2032deoxyuridine (EdU) made it possible to correlate the extent of DNA replication during the pulse with the extent of the UV\u2010induced H2AX phosphorylation within the same cells. This correlation was very strong (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup> = 0.98) and the cells that did not incorporate EdU showed no evidence of H2AX phosphorylation. The data are consistent with the mechanism in which stalling of DNA replication forks upon collision with the primary UV\u2010induced DNA lesions and likely formation of double\u2010strand DNA breaks triggers DDR. The prior reports (including our own) on induction of \u03b3H2AX in G<jats:sub>1<\/jats:sub> cells by UV may have erroneously identified cells initiating DNA replication following UV exposure as G<jats:sub>1<\/jats:sub> cells due to the fact that their DNA content did not significantly differ from that of G<jats:sub>1<\/jats:sub> cells that had not initiated DNA replication. \u00a9 2009 International Society for Advancement of Cytometry<\/jats:p>","DOI":"10.1002\/cyto.a.20839","type":"journal-article","created":{"date-parts":[[2009,12,14]],"date-time":"2009-12-14T21:24:06Z","timestamp":1260825846000},"page":"285-293","source":"Crossref","is-referenced-by-count":51,"title":["Kinetics of the UV\u2010induced DNA damage response in relation to cell cycle phase. 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