Chromatin dynamics during DSB repair

We show that double strand breaks (DSBs) induced in chromatin of low as well as high density by exposure of human cells to gamma-rays repaired in low-density chromatin. Extensive chromatin decondensation manifested in the vicinity of DSBs by decreased intensity chromatin labelling, increased H4K5 acetylation, and decreased H3K9 dimethylation was observed already 15 min after irradiation. slight movement of sporadic DSB loci for short distances was noticed in living cells associated with chromatin decondensation around This frequently resulted in their protrusion into the low-density chromatin domains. In these regions, the clustering (contact or fusion) DSB foci was seen in vivo, and in situ after cell fixation. The majority of these clustered foci were repaired within 240 min, but some them persisted in the nucleus for several days after irradiation, indicating damage that is not easily repaired. We propose that the repair DSB in clustered foci might lead to misjoining of ends and, consequently, to exchange aberrations. On the other hand, the foci that persist several days without being repaired could lead instead to cell death. (C) 2007 Elsevier B.V. All rights reserved.