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PHF8 facilitates transcription recovery following DNA double-strand break repair

Jung Eun Kim1, Xiyue Pan1, Kwan Yiu Tse1

  • 1School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong S.A.R.

Nucleic Acids Research
|August 1, 2024
PubMed

Insights

PHF8 is identified as a key enzyme that reverses repressive epigenetic marks after DNA double-strand break repair, enabling transcription to resume. This facilitates cell fate and identity maintenance during DNA damage response.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Cellular Biology

Background:

  • Transcription temporarily halts on damaged chromatin to allow DNA double-strand break (DSB) repair.
  • Mechanisms for restoring gene expression post-DSB repair are not well understood.
  • Delayed transcription recovery can negatively impact cell identity and fate.

Purpose of the Study:

  • To identify molecular mechanisms that facilitate transcription recovery after DNA double-strand break repair.
  • To investigate the role of PHF8 in reversing transcriptionally repressive epigenetic modifications.

Main Methods:

  • Utilized laser-induced DNA damage models.
  • Investigated the recruitment of PHF8 to DNA damage sites.
  • Assessed the impact of PHF8 on H3K9me2 levels and transcription resumption.
  • Examined PHF8's role in ribosomal DNA (rDNA) transcription recovery.

Main Results:

  • PHF8 acts as a demethylase, reversing repressive epigenetic marks (H3K9me2) deposited by the DYRK1B-EHMT2 pathway.
  • PHF8 localizes to DNA damage sites in a DYRK1B-dependent manner.
  • PHF8 promotes the timely resolution of H3K9me2, facilitating transcription recovery.
  • PHF8 aids in the recovery of rDNA transcription after nucleolar DSBs.

Conclusions:

  • PHF8 is a crucial mediator coordinating transcription during the recovery phase of DNA double-strand break responses.
  • PHF8's demethylase activity is essential for restoring gene expression and maintaining cellular homeostasis after DNA damage.

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