The E3 ligase RFWD3 stabilizes ORC in a p53-dependent manner

Rosaline Y.C. Hsu, Sumanprava Giri, Yating Wang, Yo Chuen Lin, Dazhen Liu, Susan Wopat, Arindam Chakraborty, Kannanganattu V. Prasanth, Supriya Gangadharan Prasanth

Research output: Contribution to journalArticlepeer-review

Abstract

RFWD3 is an E3 ubiquitin ligase that plays important roles in DNA damage response and DNA replication. We have previously demonstrated that the stabilization of RFWD3 by PCNA at the replication fork enables ubiquitination of the single-stranded binding protein, RPA and its subsequent degradation for replication progression. Here, we report that RFWD3 associates with the Origin Recognition Complex (ORC) and ORC-Associated (ORCA/LRWD1), components of the pre-replicative complex required for the initiation of DNA replication. Overexpression of ORC/ORCA leads to the stabilization of RFWD3. Interestingly, RFWD3 seems to stabilize ORC/ORCA in cells expressing wild type p53, as the depletion of RFWD3 reduces the levels of ORC/ORCA. Further, the catalytic activity of RFWD3 is required for the stabilization of ORC. Our results indicate that the RFWD3 promotes the stability of ORC, enabling efficient pre-RC assembly.

Original languageEnglish (US)
Pages (from-to)2927-2938
Number of pages12
JournalCell Cycle
Volume19
Issue number21
DOIs
StatePublished - Nov 2020

Keywords

  • ORC
  • ORCA/LRWD1
  • p53
  • replication
  • RFWD3
  • ubiquitination

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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