| First Author | Revet I | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 21 | Pages | 8663-7 |
| PubMed ID | 21555580 | Mgi Jnum | J:171890 |
| Mgi Id | MGI:5002372 | Doi | 10.1073/pnas.1105866108 |
| Citation | Revet I, et al. (2011) Functional relevance of the histone {gamma}H2Ax in the response to DNA damaging agents. Proc Natl Acad Sci U S A 108(21):8663-7 |
| abstractText | The phosphorylation of H2Ax on its S139 site, gammaH2Ax, is important during DNA double-strand repair and is considered necessary for assembly of repair complexes, but its functional role after other kinds of DNA damage is less clear. We have measured the survival of isogenic mouse cell lines with the H2Ax gene knocked out, and replaced with wild-type or mutant (S139A) H2Ax genes, exposed to a range of agents with varied mechanisms of DNA damage. Knockout and mutant cells were sensitive to gamma-rays, etoposide, temozolamide, and endogenously generated reactive oxygen species, each of which can include double-strand breaks among their spectra of DNA lesions. The absence or mutation of H2Ax had no influence on sensitivity to cisplatin or mitomycin C. Although UV light induced the highest levels of gammaH2Ax, mutation of S139 had no influence on UV sensitivity or the UV DNA damage response. Complete loss of H2Ax reduced the survival of cells exposed to UV light and reduced pChk1 induction, suggesting that sites other than S139 may impact the ATR-pChk1 pathway. The relative intensity of gammaH2Ax measured in Western blots in wild-type cells did not correlate with the functional importance of gammaH2Ax. The use of gammaH2Ax as a general biomarker of DNA damage is therefore potentially misleading because it is not an unambiguous indicator of double-strand breaks, and a significant fraction of DNA repair, especially involving nucleotide excision or crosslink repair, can occur without functional involvement of gammaH2Ax. |
