Responding to chromosomal breakage during M-phase: insights from a cell-free system

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Published on: August 19, 2014

Eloise Smith1, Vincenzo Costanzo

  • 1Genome Stability Unit, London Research Institute, Clare Hall Laboratories, South Mimms, London, UK, EN6 3LD. Vincenzo.Costanzo@cancer.org.uk.

Cell Division
|July 16, 2009
PubMed

Insights

DNA double strand breaks trigger a checkpoint that delays spindle assembly by phosphorylating XCEP63. This ATM/ATR pathway regulates centrosome function during mitosis, aiding DNA repair and survival.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • DNA double-strand breaks (DSBs) activate ATM and ATR kinases, initiating cell cycle checkpoints to prevent mitosis.
  • The response of cells to DSBs occurring during mitosis remains largely unknown.
  • The Xenopus egg extract system is a powerful tool for studying cell cycle regulation and DNA damage responses.

Discussion:

  • A novel ATM and ATR dependent checkpoint impacting centrosome-driven spindle assembly has been identified using Xenopus egg extracts.
  • XCEP63, a centrosome-localized protein crucial for spindle assembly, is a key target of this pathway.
  • ATM and ATR directly phosphorylate XCEP63 at serine 560, causing its delocalization from the centrosome.

Key Insights:

  • Mitotic DSBs induce a checkpoint that delays spindle assembly via XCEP63 phosphorylation and delocalization.
  • This pathway regulates centrosome function during mitosis in response to DNA damage.
  • The identified mechanism is essential for proper spindle assembly and mitotic progression.

Outlook:

  • This pathway may play a role in DNA repair during mitosis.
  • Investigating this checkpoint could reveal new strategies for mitotic cell survival in the presence of chromosome breakage.
  • Further research in Xenopus egg extracts can elucidate conserved mechanisms of DNA damage response in mitosis.

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