Down-regulation of Ku autoantigen, DNA-dependent protein kinase, and poly(ADP-ribose) polymerase during cellular

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A Salminen1, M Helenius, T Lahtinen

  • 1Department of Neuroscience and Neurology, University of Kuopio, Finland. antero.salminen@uku.fi

Biochemical and Biophysical Research Communications
|October 23, 1997
PubMed

Insights

Cellular senescence and quiescence down-regulate DNA damage recognition proteins, including Ku autoantigens, DNA-dependent protein kinase, and poly (ADP-ribose) polymerase, potentially increasing DNA damage accumulation during aging.

Area of Science:

  • Cellular and Molecular Biology
  • Aging Research
  • DNA Repair Mechanisms

Background:

  • Accumulation of DNA mutations is a hallmark of aging and cellular senescence.
  • Ku autoantigens, DNA-dependent protein kinase (DNA-PK), and poly (ADP-ribose) polymerase (PARP) are crucial for recognizing DNA damage.
  • Understanding how senescence affects these DNA repair components is vital for aging research.

Purpose of the Study:

  • To investigate the impact of replicative senescence and cellular quiescence on key DNA damage recognition proteins in human fibroblasts.
  • To compare protein levels and enzyme activities in senescent, quiescent, and immortalized cells.

Main Methods:

  • Comparison of presenescent, replicatively senescent, SV-40 immortalized, and serum-deficient quiescent human WI-38 fibroblasts.
  • Quantification of nuclear Ku autoantigen components (p70, p86) using Western blotting.
  • Assay of DNA-dependent protein kinase activity.
  • Measurement of poly (ADP-ribose) polymerase (PARP) protein levels.

Main Results:

  • Replicative senescence significantly decreased nuclear p70 and p86 Ku autoantigen levels.
  • SV-40 immortalization and quiescence did not alter p86 levels but slightly increased p70.
  • Both replicative senescence and quiescence reduced DNA-PK activity, while SV-40 immortalization increased it.
  • Replicative senescence and quiescence strongly decreased PARP protein levels.
  • No apoptosis was observed in replicatively senescent cells.

Conclusions:

  • Replicative senescence and, to some extent, cellular quiescence down-regulate the DNA damage recognition system involving Ku autoantigens, DNA-PK, and PARP.
  • This down-regulation may contribute to enhanced DNA damage accumulation during the aging process.
  • These findings highlight potential mechanisms linking senescence to age-related genomic instability.

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