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

Nobuo Horikoshi, Dharmendra Sharma, Fransisca Leonard, Raj K. Pandita, Vijaya K. Charaka, Shashank Hambarde, Nobuko T. Horikoshi, Puja Gaur Khaitan, Sharmistha Chakraborty, Jacques Cote, Biana Godin, Clayton R. Hunt, Tej K. Pandita*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

The 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.

Original languageEnglish (US)
Article number253
JournalCommunications Biology
Volume2
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Fingerprint

Dive into the research topics of 'Pre-existing H4K16ac levels in euchromatin drive DNA repair by homologous recombination in S-phase'. Together they form a unique fingerprint.

Cite this