γH2AX in the S Phase after UV Irradiation Corresponds to the Sites of DNA Replication and Not DNA Damage
21 Pages Posted: 13 Jan 2020 Sneak Peek Status: Under ReviewMore...
Ultraviolet (UV) radiation is a major environmental mutagen. Exposure to UV leads to a sharp peak of γH2AX — the phosphorylated form of a histone variant H2AX — in the S phase cells within a population. γH2AX has been considered as a definitive marker of DNA damage inside a cell. In this report we show that the γH2AX peak in the S phase after UV irradiation does not report on the extent of DNA damage. Instead it corresponds to the accumulation of γH2AX at the sites of active replication at the time of UV irradiation. We further show that these colocalization sites do not correspond to stalled replication forks — DNA synthesis is still carried on there, albeit at slower speeds. In fact, most of the S phase cells at the time of UV irradiation complete the replication of their DNA and later arrest in the G2 phase of the cell cycle. The study poses new questions as to the roles of γH2AX in the maintenance of genome stability at the replication forks by challenging the conventional idea of γH2AX as simply a mediator and hence a marker of DNA damage and subsequent repair.
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