Dissemin is shutting down on January 1st, 2025

Published in

Nature Research, Communications Biology, 1(2), 2019

DOI: 10.1038/s42003-019-0498-z

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Pre-existing H4K16ac levels in euchromatin drive DNA repair by homologous recombination in S-phase

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Preprint: archiving allowed
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Postprint: archiving forbidden
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Published version: archiving allowed
Data provided by SHERPA/RoMEO

Abstract

AbstractThe homologous recombination (HR) repair pathway maintains genetic integrity after DNA double-strand break (DSB) damage and is particularly crucial for maintaining fidelity of expressed genes. Histone H4 acetylation on lysine 16 (H4K16ac) is associated with transcription, but how pre-existing H4K16ac directly affects DSB repair is not known. To answer this question, we used CRISPR/Cas9 technology to introduce I-SceI sites, or repair pathway reporter cassettes, at defined locations within gene-rich (high H4K16ac/euchromatin) and gene-poor (low H4K16ac/heterochromatin) regions. The frequency of DSB repair by HR is higher in gene-rich regions. Interestingly, artificially targeting H4K16ac at specific locations using gRNA/dCas9-MOF increases HR frequency in euchromatin. Finally, inhibition/depletion of RNA polymerase II or Cockayne syndrome B protein leads to decreased recruitment of HR factors at DSBs. These results indicate that the pre-existing H4K16ac status at specific locations directly influences the repair of local DNA breaks, favoring HR in part through the transcription machinery.