First published online March 7, 2007
Journal of Cell Science 120, 602e (2007)
© The Company of Biologists Limited
Histone H2AX minds the gap
DNA damage must be rapidly detected and repaired to avoid genomic instability. In human cells, the ATM (ataxia-telangiectasia mutated) protein phosphorylates histone H2AX at double-stranded DNA breaks; the phosphorylated histone then tethers DNA-repair proteins at the break. Replication stress caused by UV irradiation also induces H2AX phosphorylation – this time by ATR (ATM and Rad-3 related) – in cycling cells, but what happens in quiescent cells exposed to UV irradiation? Tsukasa Matsunaga and colleagues now report that ATR-dependent H2AX phosphorylation also occurs in quiescent human cells after UV irradiation but via a distinct pathway (see p. 1104). Their experiments indicate that low levels of replication factors cause the perturbation of nucleotide excision repair (the major system for removing UV-induced DNA lesions) at a gap-filling step, which leads to the formation of single-stranded DNA gaps and the subsequent phosphorylation of H2AX by ATR. Because most cells do not cycle in vivo, this route to H2AX phosphorylation could be crucial for the maintenance of genomic stability in many tissues.
Related articles in JCS:
- Perturbed gap-filling synthesis in nucleotide excision repair causes histone H2AX phosphorylation in human quiescent cells
- Megumi Matsumoto, Kie Yaginuma, Ai Igarashi, Mayumi Imura, Mizuho Hasegawa, Kuniyoshi Iwabuchi, Takayasu Date, Toshio Mori, Kanji Ishizaki, Katsumi Yamashita, Manabu Inobe, and Tsukasa Matsunaga
JCS 2007 120: 1104-1112.
[Abstract]
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