[Effects of overexpression of human pol-beta on cellular response to DNA damage]

Liu-tao Du1, Lei Xu, Xing-fen Yang

  • 1Department of Health Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.

Abstract

Insights

Overexpression of human DNA polymerase (pol-beta) reduces cellular DNA damage from methyl methanesulfonate (MMS). However, high pol-beta levels increase error-prone DNA synthesis during repair, leading to higher mutation rates.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • DNA polymerase beta (Pol-beta) plays a crucial role in DNA repair pathways.
  • Understanding the impact of Pol-beta levels on cellular responses to DNA damage is essential for comprehending genome stability.

Purpose of the Study:

  • To investigate the biological effects of overexpressing human DNA polymerase beta (Pol-beta) on cellular responses to DNA damage.

Main Methods:

  • Generated a cell strain (HLFbeta) with stable overexpression of human Pol-beta.
  • Exposed HLFbeta cells and control cells to methyl methanesulfonate (MMS) to assess DNA damage, cell cycle distribution, and mutation rates.

Main Results:

  • HLFbeta cells exhibited significantly lower DNA damage levels compared to control cells when exposed to MMS.
  • Overexpression of Pol-beta led to increased G1 and G2 phase cell cycle arrest in response to MMS.
  • MMS-induced mutagenesis rate was significantly higher in HLFbeta cells compared to control cells.

Conclusions:

  • Elevated Pol-beta levels reduce cellular DNA damage induced by MMS.
  • Overexpression of Pol-beta enhances error-prone DNA synthesis during the DNA repair process, increasing mutation frequency.

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