Frontiers in Oncology (Apr 2022)

Chk1 Inhibition Hinders the Restoration of H3.1K56 and H3.3K56 Acetylation and Reprograms Gene Transcription After DNA Damage Repair

  • Nan Ding,
  • Nan Ding,
  • Nan Ding,
  • Nan Ding,
  • Zhiang Shao,
  • Zhiang Shao,
  • Fangyun Yuan,
  • Pei Qu,
  • Pei Qu,
  • Ping Li,
  • Ping Li,
  • Ping Li,
  • Ping Li,
  • Dong Lu,
  • Dong Lu,
  • Jufang Wang,
  • Jufang Wang,
  • Qianzheng Zhu,
  • Qianzheng Zhu

DOI
https://doi.org/10.3389/fonc.2022.862592
Journal volume & issue
Vol. 12

Abstract

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H3K56 acetylation (H3K56Ac) was reported to play a critical role in chromatin assembly; thus, H3K56ac participates in the regulation of DNA replication, cell cycle progression, DNA repair, and transcriptional activation. To investigate the influence of DNA damage regulators on the acetylation of histone H3 and gene transcription, U2OS cells expressing SNAP-labeled H3.1 or SNAP-labeled H3.3 were treated with ATM, ATR, or a Chk1 inhibitor after ultraviolet (UV) radiation. The levels of H3.1K56ac, H3.3K56ac, and other H3 site-specific acetylation were checked at different time points until 24 h after UV radiation. The difference in gene transcription levels was also examined by mRNA sequencing. The results identified Chk1 as an important regulator of histone H3K56 acetylation in the restoration of both H3.1K56ac and H3.3K56ac. Moreover, compromising Chk1 activity via chemical inhibitors suppresses gene transcription after UV radiation. The study suggests a previously unknown role of Chk1 in regulating H3K56 and some other site-specific H3 acetylation and in reprograming gene transcription during DNA damage repair.

Keywords