Premium
SET 8 methyltransferase activity during the DNA double‐strand break response is required for recruitment of 53 BP 1
Author(s) -
Dulev Stanimir,
Tkach Johnny,
Lin Sichun,
Batada Nizar N
Publication year - 2014
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201439434
Subject(s) - chromatin , dna damage , dna , dna repair , histone , microbiology and biotechnology , methyltransferase , dna methylation , homologous recombination , biology , chemistry , genetics , methylation , gene , gene expression
Abstract DNA double‐strand breaks ( DSB s) activate a signaling pathway known as the DNA damage response ( DDR ) which via protein–protein interactions and post‐translational modifications recruit signaling proteins, such as 53 BP 1, to chromatin flanking the lesion. Depletion of the SET 8 methyltransferase prevents accumulation of 53 BP 1 at DSB s; however, this phenotype has been attributed to the role of SET 8 in generating H4K20 methylation across the genome, which is required for 53 BP 1 binding to chromatin, prior to DNA damage. Here, we report that SET 8 acts directly at DSB s during the DNA damage response ( DDR ). SET 8 accumulates at DSB s and is enzymatically active at DSB s. Depletion of SET 8 just prior to the induction of DNA damage abrogates 53 BP 1's accumulation at DSB s, suggesting that SET 8 acts during DDR . SET 8's occupancy at DSB s is regulated by histone deacetylases ( HDAC s). Finally, SET 8 is functionally required for efficient repair of DSB s specifically via the non‐homologous end‐joining pathway ( NHEJ ). Our findings reveal that SET 8's active role during DDR at DSB s is required for 53 BP 1's accumulation.