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Study of the DNA Damage Checkpoint using Xenopus Egg Extracts
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DdcA antagonizes a bacterial DNA damage checkpoint.

Peter E Burby1, Zackary W Simmons1, Lyle A Simmons1

  • 1Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.

Molecular Microbiology
|October 14, 2018
PubMed
Summary

Bacteria use a checkpoint to halt cell division when DNA is damaged. New research reveals DdcA regulates this process by controlling the YneA protein, independent of degradation, uncovering a novel checkpoint control mechanism.

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Area of Science:

  • Microbiology
  • Molecular Biology
  • Cell Biology

Background:

  • Bacteria coordinate DNA replication and cell division for genetic inheritance.
  • DNA damage triggers a cell cycle checkpoint via a division inhibitor.
  • Current models emphasize protease-mediated inhibitor degradation for checkpoint regulation.

Purpose of the Study:

  • To investigate the role of the newly identified gene ddcA in bacterial DNA damage response.
  • To elucidate the mechanism by which DdcA influences the cell cycle checkpoint.

Main Methods:

  • Genome-wide screens to identify genes critical for DNA damage survival.
  • Genetic approaches including gene deletion and overexpression.
  • Analysis of YneA protein levels, stability, and localization using functional fusions.

Main Results:

  • Deletion of ddcA confers sensitivity to DNA damage, dependent on the checkpoint protein YneA.
  • DdcA function is distinct from known checkpoint recovery proteases.
  • DdcA regulates YneA independently of protein degradation and localization, preventing YneA-dependent cell elongation.

Conclusions:

  • DdcA plays a novel role in the DNA damage checkpoint activation in Bacillus subtilis.
  • DdcA helps establish the YneA threshold required for checkpoint initiation.
  • This identifies a new regulatory step in bacterial DNA damage response.