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UHRF1 depletion causes a G2/M arrest, activation of DNA damage response and apoptosis

Amy L Tien1, Sucharita Senbanerjee, Atul Kulkarni

  • 1Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

The Biochemical Journal
|January 11, 2011
PubMed

Insights

Depleting UHRF1 (ubiquitin-like protein, containing PHD and RING finger domains 1) in cancer cells activates DNA damage response, arrests the cell cycle, and induces apoptosis. UHRF1 links epigenetic regulation to DNA replication.

Area of Science:

  • Epigenetics
  • Cell Biology
  • Cancer Research

Background:

  • UHRF1 (ubiquitin-like protein, containing PHD and RING finger domains 1) is crucial for cell cycle progression and epigenetic regulation.
  • Its precise role in DNA damage response and repair remains incompletely understood.

Purpose of the Study:

  • To investigate the consequences of UHRF1 depletion on DNA damage response, cell cycle progression, and apoptosis in cancer cells.
  • To elucidate the role of UHRF1 in DNA damage repair and its link to epigenetic regulation.

Main Methods:

  • Depletion of UHRF1 in cancer cell lines.
  • Analysis of DNA damage response markers (e.g., phosphorylated histone H2AX, CHK2, CDC25, CDK1).
  • Assessment of cell cycle distribution and apoptosis induction (caspase-dependent).

Main Results:

  • UHRF1 depletion triggered DNA damage response, G2/M cell cycle arrest, and caspase 8-dependent apoptosis.
  • Accumulation of UHRF1 at DNA damage sites suggests a role in repair.
  • Apoptosis and cell cycle arrest occurred independently of p53 status.
  • Caspase 8 depletion inhibited UHRF1 knockdown-induced cell death.

Conclusions:

  • UHRF1 plays a critical role in maintaining genomic stability by linking epigenetic regulation with DNA replication and repair.
  • UHRF1 depletion activates a DNA damage response pathway leading to cell cycle arrest and apoptosis, highlighting its potential as a therapeutic target in cancer.

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