A New Mode of Mitotic Surveillance

Trends Cell Biol. 2017 May;27(5):314-321. doi: 10.1016/j.tcb.2017.01.004. Epub 2017 Feb 7.

Abstract

Cells have evolved certain precautions to preserve their genomic content during mitosis and avoid potentially oncogenic errors. Besides the well-established DNA damage checkpoint and spindle assembly checkpoint (SAC), recent observations have identified an additional mitotic failsafe referred to as the mitotic surveillance pathway. This pathway triggers a cell cycle arrest to block the growth of potentially unfit daughter cells and is activated by both prolonged mitosis and centrosome loss. Recent genome-wide screens surprisingly revealed that 53BP1 and USP28 act upstream of p53 to mediate signaling through the mitotic surveillance pathway. Here we review advances in our understanding of this failsafe and discuss how 53BP1 and USP28 adopt noncanonical roles to function in this pathway.

Keywords: cell cycle arrest; centrosome; checkpoint; mitosis; surveillance.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Cycle Checkpoints
  • Centrosome / metabolism
  • Humans
  • Mitosis*
  • Models, Biological
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor p53-Binding Protein 1 / metabolism

Substances

  • Tumor Suppressor Protein p53
  • Tumor Suppressor p53-Binding Protein 1