DMCA
Megabase chromatin domains involved in DNA double-strand breaks in vivo (1999)
| Venue: | J. Cell |
| Citations: | 202 - 2 self |
BibTeX
@ARTICLE{Rogakou99megabasechromatin,
author = {Emmy P. Rogakou and Chye Boon and Christophe Redon and William M. Bonner},
title = {Megabase chromatin domains involved in DNA double-strand breaks in vivo},
journal = {J. Cell},
year = {1999},
pages = {146--905}
}
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Abstract
Abstract. The loss of chromosomal integrity from DNA double-strand breaks introduced into mammalian cells by ionizing radiation results in the specific phosphorylation of histone H2AX on serine residue 139, yielding a specific modified form named �-H2AX. An antibody prepared to the unique region of human �-H2AX shows that H2AX homologues are phosphorylated not only in irradiated mammalian cells but also in irradiated cells from other species, including Xenopus laevis, Drosophila melanogaster, and Saccharomyces cerevisiae. The antibody reveals that �-H2AX appears as discrete nuclear foci within 1 min after exposure of cells to ionizing radiation. The numbers of these foci are comparable to the numbers of induced DNA double-strand breaks. When DNA double-strand breaks are introduced into specific partial nuclear volumes of cells by means of a pulsed microbeam laser, �-H2AX foci form at these sites. In mitotic cells from cultures exposed to nonlethal amounts of ionizing radiation, �-H2AX foci form band-like structures on chromosome arms and on the end of broken arms. These results offer direct visual confirmation that �-H2AX forms en masse at chromosomal sites of DNA doublestrand breaks. The results further suggest the possible existence of units of higher order chromatin structure involved in monitoring DNA integrity. Key words: ionizing radiation • histone H2AX • DNA double-strand breaks • phosphorylation • indirect immunofluorescence THE universal presence of ionizing radiation poses a constant threat to the chromosomal integrity of living organisms. One of the most serious cellular lesions induced by radiation is the random DNA doublestrand break. This lesion jeopardizes a chromosome’s physical integrity, which is essential for its correct segregation during mitosis and meiosis, as well as its informational redundancy, which is critical for maintaining accurate encoding of cellular components. Thus, it is not surprising that multiple mechanisms exist for dealing with this serious lesion, including nonhomologous end-joining, homologous recombination, and apoptosis (Jeggo, 1998; Kanaar
Keyphrases
dna double-strand break megabase chromatin domain chromosomal integrity induced dna double-strand break chromosome physical integrity h2ax form form band-like structure cellular component nonlethal amount mitotic cell saccharomyces cerevisiae human h2ax radiation result informational redundancy histone h2ax mammalian cell unique region correct segregation dna integrity order chromatin structure possible existence homologous recombination accurate encoding multiple mechanism irradiated cell h2ax homologues dna doublestrand break specific partial nuclear volume specific modified form xenopus laevis constant threat serious lesion drosophila melanogaster broken arm chromosome arm serious cellular lesion irradiated mammalian cell living organism nonhomologous end-joining random dna doublestrand break discrete nuclear focus key word specific phosphorylation pulsed microbeam laser chromosomal site direct visual confirmation
