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p97/VCP- and Lys48-linked polyubiquitination form a new signaling pathway in DNA damage response

Kristijan Ramadan1

  • 1Institute of Pharmacology and Toxicology, University of Zürich-Vetsuisse, Zürich, Switzerland. kristijan.ramadan@vetpharm.uzh.ch

Cell Cycle (Georgetown, Tex.)
|March 7, 2012
PubMed

Insights

A new DNA damage response pathway involving RNF8-dependent Lys48-linked polyubiquitin chains and p97/VCP segregase activity has been discovered. This pathway is crucial for protein turnover and regulating DNA double-strand break repair.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • DNA double-strand breaks (DSBs) trigger cellular responses to maintain genome stability.
  • The RNF8/RNF168-dependent Lys63-linked polyubiquitination pathway was considered the primary mechanism in the DNA damage response (DDR).

Purpose of the Study:

  • To investigate the role of a newly identified ubiquitin-signaling pathway in DSB repair.
  • To elucidate the function of RNF8-dependent Lys48-linked polyubiquitin chains and p97/VCP segregase activity in the DDR.

Main Methods:

  • The study discusses the involvement of ubiquitin-dependent p97/VCP segregase activity.
  • Analysis of RNF8-dependent Lys48-linked polyubiquitin chains at DSB sites.

Main Results:

  • A parallel ubiquitin-signaling DDR pathway involving RNF8-dependent Lys48-linked polyubiquitin chains and p97/VCP segregase has been identified.
  • This pathway is essential for spatiotemporal protein turnover at DSB sites.
  • It regulates both homologous recombination and nonhomologous end joining repair pathways.

Conclusions:

  • The RNF8/Lys48 polyubiquitin chains/p97 pathway represents a critical component of the DNA damage response.
  • This pathway plays a significant role in regulating protein turnover and coordinating DSB repair.
  • Further investigation into p97's chromatin-related functions in DSB repair is warranted.

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