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

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

doi:10.3389/fonc.2022.862592

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

Front Oncol. 2022 Apr 14:12:862592. doi: 10.3389/fonc.2022.862592. eCollection 2022.

Authors

Nan Ding^{1

2

3

4}, Zhiang Shao^{1

2}, Fangyun Yuan⁵, Pei Qu^{1

2}, Ping Li^{1

2

3

4}, Dong Lu^{1

2}, Jufang Wang^{1

2}, Qianzheng Zhu^{3

4}

Affiliations

¹ Key Laboratory of Space Radiobiology of Gansu Province and Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.
² College of Life Science, University of Chinese Academy of Sciences, Beijing, China.
³ Department of Radiology and Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH, United States.
⁴ James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH, United States.
⁵ Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, China.

Abstract

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: Chk1; H3K56 acetylation; chromatin assembly; posttranslational modification (PMT); radiation.

Grants and funding

R01 ES012991/ES/NIEHS NIH HHS/United States