RNF8- and Ube2S-Dependent Ubiquitin Lysine 11-Linkage Modification in Response to DNA Damage

Atanu Paul, Bin Wang

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Ubiquitin modification of proteins plays pivotal roles in the cellular response to DNA damage. Given the complexity of ubiquitin conjugation due to the formation of poly-conjugates of different linkages, functional roles of linkage-specific ubiquitin modification at DNA damage sites are largely unclear. We identify that Lys11-linkage ubiquitin modification occurs at DNA damage sites in an ATM-dependent manner, and ubiquitin-modifying enzymes, including Ube2S E2-conjugating enzyme and RNF8 E3 ligase, are responsible for the assembly of Lys11-linkage conjugates on damaged chromatin, including histone H2A/H2AX. We show that RNF8- and Ube2S-dependent Lys11-linkage ubiquitin conjugation plays an important role in regulating DNA damage-induced transcriptional silencing, distinct from the role of Lys63-linkage ubiquitin in the recruitment of DNA damage repair proteins 53BP1 and BRCA1. Thus, our study highlights the importance of linkage-specific ubiquitination at DNA damage sites, and it reveals that Lys11-linkage ubiquitin modification plays a crucial role in the DNA damage response.

Original languageEnglish (US)
Pages (from-to)458-472.e5
JournalMolecular cell
Volume66
Issue number4
DOIs
StatePublished - May 18 2017

Keywords

  • DNA damage response
  • RNF8
  • Ube2S
  • double strand breaks
  • histone H2A/H2AX
  • ionizing radiation
  • transcription inhibition
  • ubiquitin
  • ubiquitin lysine 11-linkage
  • ubiquitin lysine 63-linkage

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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