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Human MutY homolog induces apoptosis in etoposide-treated HEK293 cells

Soo-Hyun Hahm1, Ji Hyung Chung, Lia Agustina

  • 1Department of Advanced Technology Fusion, Konkuk University, Gwangjin-gu, Seoul 143-701;

Oncology Letters
|December 11, 2012
PubMed

Insights

Human MutY homolog (hMYH) acts as a sensor for etoposide (ETP)-induced apoptosis. Without hMYH, cells fail to recognize DNA damage, preventing activation of the ATR pathway, crucial for cell survival signaling.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • DNA Damage Response

Background:

  • Etoposide (ETP) is a chemotherapeutic agent that induces DNA damage.
  • The ataxia telangiectasia mutated (ATM) and Rad3-related protein (ATR) pathway is critical for cellular response to DNA damage.
  • Human MutY homolog (hMYH) is involved in DNA repair.

Purpose of the Study:

  • To investigate the role of hMYH in etoposide-induced apoptosis.
  • To elucidate the interaction between hMYH, ATR, and TopBP1 during DNA damage response.
  • To understand how hMYH depletion affects apoptotic signaling and ATR pathway activation.

Main Methods:

  • Depletion of ATM, ATR, TopBP1, and hMYH using knockdown techniques.
  • Treatment of cells with etoposide (ETP).
  • Analysis of apoptotic signaling.
  • Assessment of protein-protein interactions (ATR, TopBP1, hMYH) using co-immunoprecipitation.

Main Results:

  • ETP treatment of ATM, ATR, TopBP1, and hMYH-depleted cells significantly reduced apoptotic signaling.
  • ETP treatment increased the association between ATR or TopBP1 and hMYH.
  • In hMYH knockdown cells, ETP treatment decreased the interaction between ATR and TopBP1, indicating impaired ATR pathway activation.

Conclusions:

  • hMYH functions as a sensor for ETP-induced apoptosis.
  • In the absence of hMYH, cells are impaired in recognizing DNA damage signals.
  • hMYH depletion prevents the activation of the ATR pathway, impacting cellular survival.

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