Nucleosome disassembly during human non-homologous end joining followed by concerted HIRA- and CAF-1-dependent reassembly.
The cell achieves DNA double-strand break (DSB) repair in the context of chromatin structure. However, the mechanisms used to expose DSBs to the repair machinery and to restore the chromatin organization after repair remain elusive. Here we show that induction of a DSB in human cells causes local nucleosome disassembly, apparently independently from DNA end resection. This efficient removal of histone H3 from the genome during non-homologous end joining was promoted by both ATM and the ATP-dependent nucleosome remodeler INO80. Chromatin reassembly during DSB repair was dependent on the HIRA histone chaperone that is specific to the replication-independent histone variant H3.3 and on CAF-1 that is specific to the replication-dependent canonical histones H3.1/H3.2. Our data suggest that the epigenetic information is re-established after DSB repair by the concerted and interdependent action of replication-independent and replication-dependent chromatin assembly pathways.
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, United States.
Xuan
X
Li
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, United States.
Jessica K
0000-0001-9765-1659
JK
Tyler
D000074183:ATPases Associated with Diverse Cellular Activities; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D056504:Chromatin Assembly Factor-1 / Q000378:metabolism*; D059766:DNA End-Joining Repair; D004265:DNA Helicases / Q000378:metabolism; D004268:DNA-Binding Proteins; D057809:HEK293 Cells; D056488:Histone Chaperones / Q000378:metabolism*; D006801:Humans; D009707:Nucleosomes / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
C489780:CNOT8 protein, human; D018797:Cell Cycle Proteins; D056504:Chromatin Assembly Factor-1; D004268:DNA-Binding Proteins; C086057:HIRA protein, human; D056488:Histone Chaperones; D009707:Nucleosomes; D014157:Transcription Factors; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C524421:INO80 protein, human
DSB repair; H3.3; NHEJ; assembly; chromatin; chromosomes; disassembly; genes; human