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

• Published in: Genome research 2021-05, Vol.31 (5), p.775-788
• Main Authors: Tripuraneni, Vinay, Memisoglu, Gonen, MacAlpine, Heather K, Tran, Trung Q, Zhu, Wei, Hartemink, Alexander J, Haber, James E, MacAlpine, David M
• Format: Article
• Language: English
• Subjects: Chromatin; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA Breaks, Double-Stranded; DNA End-Joining Repair; DNA Repair; DNA Replication - genetics; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Double-strand break repair; Histones; MRE11 protein; Non-homologous end joining; Nucleosomes; Nucleosomes - genetics; Replication; Yeast
• ISSN: 1088-9051; 1549-5469
• DOI: 10.1101/gr.271155.120

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 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.