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Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

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The co-repressor SMRT delays DNA damage-induced caspase activation by repressing pro-apoptotic genes and modulating

Claudio Scafoglio1, Marcus Smolka, Huilin Zhou

  • 1Howard Hughes Medical Institute and School of Medicine, University of California San Diego, La Jolla, California, United States of America. cscafoglio@mednet.ucla.edu

Plos One
|May 22, 2013
PubMed

Insights

Checkpoint kinase 2 (Chk2) regulates DNA damage response. New findings show Chk2 interacts with co-regulators to control cell death, impacting DNA repair timing.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Checkpoint kinase 2 (Chk2) is a key regulator of the DNA damage response.
  • Chk2 influences cellular fate, directing cells towards either survival/repair or apoptosis.

Purpose of the Study:

  • To identify a novel role for Chk2 in transcriptional regulation.
  • To elucidate Chk2's contribution to the balance between cell survival and apoptosis after DNA damage.

Main Methods:

  • Investigated Chk2 interactions with transcriptional co-regulator complexes.
  • Assessed the role of Chk2 and SMRT in regulating pro-apoptotic gene expression upon DNA damage.

Main Results:

  • Chk2 interacts with NCoR/SMRT co-repressor complexes.
  • Chk2 is required for SMRT recruitment to pro-apoptotic gene promoters following DNA damage.
  • SMRT represses pro-apoptotic genes, including Wip1 phosphatase, crucial for Chk2 feedback regulation.

Conclusions:

  • Chk2 plays a significant role in transcriptional regulation, influencing cell fate decisions post-DNA damage.
  • The Chk2-SMRT interaction modulates apoptosis and DNA repair timing through a feedback loop involving Wip1.

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