The centriolar satellite protein Cep131 is important for genome stability

J Cell Sci. 2012 Oct 15;125(Pt 20):4770-9. doi: 10.1242/jcs.104059. Epub 2012 Jul 13.

Abstract

The centrosome acts as a centre for microtubule organisation and plays crucial roles in cell polarity, migration, growth and division. Cep131 has recently been described as a basal body component essential for cilium formation, but its function in non-ciliogenic cells is unknown. We identified human Cep131 (also known as AZI1) in a screen for regulators of genome stability. We show that centrosomal localisation of Cep131 is cell-cycle-regulated and requires both an intact microtubule network and a functional dynein-dynactin transport system. Cep131 is recruited to centriolar satellites by PCM1, and localised to the centriolar core region by both pericentrin and Cep290. Depletion of Cep131 results in a reduction in proliferation rate, centriole amplification, an increased frequency of multipolar mitosis, chromosomal instability and an increase in post-mitotic DNA damage. These data therefore highlight the importance of human Cep131 for maintaining genomic integrity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / metabolism
  • Autoantigens / metabolism
  • Cell Cycle Proteins* / genetics
  • Cell Cycle Proteins* / metabolism
  • Cell Line
  • Centrioles* / genetics
  • Centrioles* / ultrastructure
  • Centrosome* / metabolism
  • Centrosome* / ultrastructure
  • Chromosomal Instability
  • Cytoskeletal Proteins
  • Dynactin Complex
  • Dyneins / metabolism
  • Genomic Instability*
  • Humans
  • Microtubule Proteins* / genetics
  • Microtubule Proteins* / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Mitosis / genetics
  • Neoplasm Proteins / metabolism

Substances

  • Antigens, Neoplasm
  • Autoantigens
  • CEP131 protein, human
  • Cell Cycle Proteins
  • Cep290 protein, human
  • Cytoskeletal Proteins
  • Dynactin Complex
  • Microtubule Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • PCM1 protein, human
  • Dyneins