Local nucleosome dynamics and eviction following a double-strand break are reversible by NHEJ-mediated repair in the absence of DNA replication.

Local nucleosome dynamics and eviction following a double-strand break are reversible by NHEJ-mediated repair in the absence of DNA replication.
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DOI:
10.1101/gr.271155.120
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发表时间:
2021-05
期刊:
影响因子:
7
通讯作者:
MacAlpine DM
MacAlpine DM
中科院分区:
生物学1区
文献类型:
--
作者:
Tripuraneni V;Memisoglu G;MacAlpine HK;Tran TQ;Zhu W;Hartemink AJ;Haber JE;MacAlpine DM

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我们询问在核苷酸分辨率的时空顺序染色质的变化,发生后立即位点特异性双链断裂(DSB)上游的PHO 5位点和其随后的修复非同源末端连接(NHEJ)。我们观察到立即驱逐的核小体侧翼的断裂和相邻的核小体的重新定位远离断裂。这些早期的染色质事件是独立的末端处理Mre 11-Rad 50-Xrs 2(MRX)复合物,并在MRX依赖的广泛驱逐组蛋白和DNA末端切除,延伸到1.8kb远离断裂之前。我们还研究了G1期阻滞人群中NHEJ介导的修复的时间动态。伴随着NHEJ的DSB修复,我们观察到核小体在其最初占据的位置上的再沉积和精确的重新定位。这种病变前染色质景观的重建表明,DNA复制独立的机制存在,以保持DSB修复后的表观基因组组织。
We interrogated at nucleotide resolution the spatiotemporal order of chromatin changes that occur immediately following a site-specific double-strand break (DSB) upstream of the PHO5 locus and its subsequent repair by nonhomologous end joining (NHEJ). We observed the immediate eviction of a nucleosome flanking the break and the repositioning of adjacent nucleosomes away from the break. These early chromatin events were independent of the end-processing Mre11-Rad50-Xrs2 (MRX) complex and preceded the MRX-dependent broad eviction of histones and DNA end-resectioning that extends up to ∼8 kb away from the break. We also examined the temporal dynamics of NHEJ-mediated repair in a G1-arrested population. Concomitant with DSB repair by NHEJ, we observed the redeposition and precise repositioning of nucleosomes at their originally occupied positions. This re-establishment of the prelesion chromatin landscape suggests that a DNA replication-independent mechanism exists to preserve epigenome organization following DSB repair.
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