New answers to the old RIDDLE: RNF168 and the DNA damage response pathway

Jessica Kelliher, Gargi Ghosal, Justin Wai Chung Leung

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

The chromatin-based DNA damage response pathway is tightly orchestrated by histone post-translational modifications, including histone H2A ubiquitination. Ubiquitination plays an integral role in regulating cellular processes including DNA damage signaling and repair. The ubiquitin E3 ligase RNF168 is essential in assembling a cohort of DNA repair proteins at the damaged chromatin via its enzymatic activity. RNF168 ubiquitinates histone H2A(X) at the N terminus and generates a specific docking scaffold for ubiquitin-binding motif-containing proteins. The regulation of RNF168 at damaged chromatin and the mechanistic implication in the recruitment of DNA repair proteins to the damaged sites remain an area of active investigation. Here, we review the function and regulation of RNF168 in the context of ubiquitin-mediated DNA damage signaling and repair. We will also discuss the unanswered questions that require further investigation and how understanding RNF168 targeting specificity could benefit the therapeutic development for cancer treatment.

Original languageEnglish (US)
Pages (from-to)2467-2480
Number of pages14
JournalFEBS Journal
Volume289
Issue number9
DOIs
StatePublished - May 2022

Keywords

  • DNA double-strand break
  • DNA repair
  • RIDDLE syndrome
  • RIDDLIN
  • ubiquitin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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