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Published on: October 5, 2012

Anti-apoptotic protein BCL2 down-regulates DNA end joining in cancer cells

Tadi Satish Kumar1, Vijayalakshmi Kari, Bibha Choudhary

  • 1Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.

The Journal of Biological Chemistry
|August 12, 2010
PubMed

Insights

Cancer cells exhibit varying DNA repair efficiency. The anti-apoptotic protein BCL2 negatively regulates DNA end joining (EJ), potentially increasing chromosomal abnormalities in cancer.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Genetics

Background:

  • Chromosomal rearrangements in cancer cells may stem from unrepaired DNA double-strand breaks (DSBs).
  • Nonhomologous DNA end joining (NHEJ) is a primary pathway for repairing DSBs in eukaryotes.

Purpose of the Study:

  • To investigate the efficiency and regulation of DNA end joining (EJ) in various cancer cell lines.
  • To explore the role of the anti-apoptotic protein BCL2 in regulating EJ.

Main Methods:

  • Utilized cell-free systems with oligomeric DNA substrates to mimic DSBs.
  • Assessed EJ efficiency across different cancer cell lines.
  • Investigated BCL2 expression levels and its interaction with KU proteins.

Main Results:

  • EJ efficiency varied among cancer cell lines without significant differences in EJ protein mechanisms or expression.
  • Cancer cells with lower EJ efficiency showed higher BCL2 expression, and vice versa.
  • BCL2 negatively impacts EJ; its removal elevated EJ, while its overexpression or addition reduced EJ.
  • BCL2 was found to interact with KU proteins in vitro and in vivo.

Conclusions:

  • The anti-apoptotic protein BCL2 negatively regulates DNA end joining (EJ) in cancer cells.
  • BCL2's interaction with KU proteins may mediate this regulation.
  • This BCL2-mediated down-regulation of EJ could contribute to increased chromosomal abnormalities observed in cancer.

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