53BP1-ACLY-SLBP-coordinated activation of replication-dependent histone biogenesis maintains genomic integrity

Ting Ting Wu, Semo Jun, Eun Ji Choi, Jiao Sun, Eun Bi Yang, Hyun Seo Lee, Sang Yong Kim, Naima Ahmed Fahmi, Qibing Jiang, Wei Zhang, Jeongsik Yong, Jung Hee Lee, Ho Jin You

Research output: Contribution to journalArticlepeer-review

Abstract

p53-binding protein 1 (53BP1) regulates the DNA double-strand break (DSB) repair pathway and maintains genomic integrity. Here we found that 53BP1 functions as a molecular scaffold for the nucleoside diphosphate kinase-mediated phosphorylation of ATP-citrate lyase (ACLY) which enhances the ACLY activity. This functional association is critical for promoting global histone acetylation and subsequent transcriptome-wide alterations in gene expression. Specifically, expression of a replication-dependent histone biogenesis factor, stem-loop binding protein (SLBP), is dependent upon 53BP1-ACLY-controlled acetylation at the SLBP promoter. This chain of regulation events carried out by 53BP1, ACLY, and SLBP is crucial for both quantitative and qualitative histone biogenesis as well as for the preservation of genomic integrity. Collectively, our findings reveal a previously unknown role for 53BP1 in coordinating replication-dependent histone biogenesis and highlight a DNA repair-independent function in the maintenance of genomic stability through a regulatory network that includes ACLY and SLBP.

Original languageEnglish (US)
Pages (from-to)1465-1483
Number of pages19
JournalNucleic acids research
Volume50
Issue number3
DOIs
StatePublished - Feb 22 2022

Bibliographical note

Publisher Copyright:
© 2022 The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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