AI Article Synopsis

  • The study investigates how chromatin structure affects the cellular response to DNA breaks and identifies key chromatin regulators involved in recovery post-DNA damage.
  • Researchers used an RNA interference library to screen for genes related to chromatin remodeling, cohesion, and histone modifications, discovering several previously unlinked to DNA damage recovery.
  • The PHD finger protein 6 (PHF6) was highlighted as a crucial regulator; its loss impairs the recovery process in G2 phase cells and is essential for effective DNA repair via non-homologous end joining.

Article Abstract

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 RNAi 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 (PHF6), a gene mutated in Börjeson-Forssman-Lehmann syndrome and leukemic cancers. We find that loss of PHF6 dramatically compromises checkpoint recovery in G2 phase cells. Moreover, PHF6 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 PHF6 is a novel DNA damage response regulator that promotes end joining-mediated repair, thereby stimulating timely recovery from the G2 checkpoint.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944915PMC
http://dx.doi.org/10.15252/embr.201948460DOI Listing

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