Chromatin dynamics during DSB repair
Chromatin dynamics during DSB repair
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DOI：
10.1016/j.bbamcr.2007.07.002
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发表时间：
2007-10-01
影响因子：
5.1
通讯作者：
Kozubek, Stanislav
中科院分区：
文献类型：
--
作者：
Falk, Martin;Lukasova, Emilie;Kozubek, Stanislav
我们发现，通过将人体细胞暴露在低密度染色质修复的伽马射线下，可在低密度和高密度染色质中诱导双链断裂（DSB）。照射后 15 分钟就观察到 DSB 附近出现广泛的染色质解缩，染色质标记强度降低、H4K5 乙酰化增加和 H3K9 二甲基化减少。在活细胞中观察到与周围染色质解凝相关的零星 DSB 基因座短距离的轻微移动，这经常导致它们突出到低密度染色质域中。在这些区域中，在体内以及细胞固定后的原位观察到聚集（接触或融合）DSB 焦点。这些聚集的病灶大部分在240分钟内被修复，但有些在照射后仍持续存在于细胞核中数天，表明损伤不易修复。我们认为，簇状焦点中的 DSB 修复可能会导致末端错误连接，从而交换像差。另一方面，持续数天而未被修复的病灶可能会导致细胞死亡。 (C) 2007 Elsevier B.V. 保留所有权利。
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.