Global chromatin compaction limits the strength of the DNA damage response.
Global chromatin compaction limits the strength of the DNA damage response.
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DOI：
10.1083/jcb.200704140
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发表时间：
2007-09-24
期刊：
影响因子：
--
通讯作者：
Fernandez-Capetillo O
中科院分区：
文献类型：
--
作者：
Murga M;Jaco I;Fan Y;Soria R;Martinez-Pastor B;Cuadrado M;Yang SM;Blasco MA;Skoultchi AI;Fernandez-Capetillo O
为了应对DNA损伤，染色质经历了一个全球性的解凝聚过程，已经提出了促进基因组监视。然而，染色质致密化对DNA损伤反应（DDR）的影响尚未直接测试，因此仍然是推测性的。我们应用两种独立的方法（一种基于小鼠胚胎干细胞与接头组蛋白H1的量减少，第二种利用组蛋白去乙酰化酶抑制剂），以显示DDR的强度在“开放”染色质的背景下被放大。H1耗尽的细胞对DNA损伤具有超抗性，并呈现超敏感的检查点，我们所显示的表型可以通过每个DNA断裂时产生的信号量增加来解释。此外，H1的减少导致端粒长度的普遍增加，这是H1在染色体结构调节中尚未认识到的作用。我们建议，在表观遗传配置的微小差异可能会占细胞间的变化，观察到的DDR的强度时，组的细胞受到挑战的DNA断裂。
In response to DNA damage, chromatin undergoes a global decondensation process that has been proposed to facilitate genome surveillance. However, the impact that chromatin compaction has on the DNA damage response (DDR) has not directly been tested and thus remains speculative. We apply two independent approaches (one based on murine embryonic stem cells with reduced amounts of the linker histone H1 and the second making use of histone deacetylase inhibitors) to show that the strength of the DDR is amplified in the context of “open” chromatin. H1-depleted cells are hyperresistant to DNA damage and present hypersensitive checkpoints, phenotypes that we show are explained by an increase in the amount of signaling generated at each DNA break. Furthermore, the decrease in H1 leads to a general increase in telomere length, an as of yet unrecognized role for H1 in the regulation of chromosome structure. We propose that slight differences in the epigenetic configuration might account for the cell-to-cell variation in the strength of the DDR observed when groups of cells are challenged with DNA breaks.
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影响因子：
56.9
作者：
Celeste, A;Petersen, S;Nussenzweig, A
通讯作者：
Nussenzweig, A
影响因子：
21.3
作者：
Jazayeri, A;Falck, J;Jackson, SP
通讯作者：
Jackson, SP
DOI：
10.1073/pnas.95.13.7445
发表时间：
1998-06-23
影响因子：
11.1
作者：
Wright, JA;Keegan, KS;Concannon, P
通讯作者：
Concannon, P
DOI：
10.1073/pnas.94.14.7423
发表时间：
1997-07-08
影响因子：
11.1
作者：
Zijlmans, JMJM;Martens, UM;Lansdorp, PM
通讯作者：
Lansdorp, PM
影响因子：
5.3
作者：
Fan, YH;Nikitina, T;Skoultchi, AI
通讯作者：
Skoultchi, AI