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PHF6 promotes non‐homologous end joining and G2 checkpoint recovery
Author(s) -
Warmerdam Daniël O,
Alonsode Vega Ignacio,
Wiegant Wouter W,
van den Broek Bram,
Rother Magdalena B,
Wolthuis Rob MF,
Freire Raimundo,
van Attikum Haico,
Medema René H,
Smits Veronique AJ
Publication year - 2019
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.201948460
Subject(s) - g2 m dna damage checkpoint , chromatin , chromatin remodeling , dna damage , biology , histone , dna repair , homologous recombination , microbiology and biotechnology , dna , cell cycle checkpoint , gene , genetics , cell cycle
The cellular response to DNA breaks is influenced by chromatin compaction. To identify chromatin regulators involved in the DNA damage response, we screened for genes that affect recovery following DNA damage using an RNA i library of chromatin regulators. We identified genes involved in chromatin remodeling, sister chromatid cohesion, and histone acetylation not previously associated with checkpoint recovery. Among these is the PHD finger protein 6 ( PHF 6), a gene mutated in Börjeson–Forssman–Lehmann syndrome and leukemic cancers. We find that loss of PHF 6 dramatically compromises checkpoint recovery in G2 phase cells. Moreover, PHF 6 is rapidly recruited to sites of DNA lesions in a PARP ‐dependent manner and required for efficient DNA repair through classical non‐homologous end joining. These results indicate that PHF 6 is a novel DNA damage response regulator that promotes end joining‐mediated repair, thereby stimulating timely recovery from the G2 checkpoint.