Eme1 is involved in DNA damage processing and maintenance of genomic stability in mammalian cells

Jacinth Abraham1, Bénédicte Lemmers, M Prakash Hande

  • 1Advanced Medical Discovery Institute, Ontario Cancer Institute, 620 University Avenue, Suite 706, Toronto, Ontario M5G 2C1, Canada.

The EMBO Journal
|November 12, 2003
PubMed

Insights

Mouse Eme1 protein, with Mus81, cleaves branched DNA structures crucial for DNA repair. Eme1 deficiency causes genomic instability, highlighting its role in maintaining genome integrity.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Eme1 protein, in complex with Mus81, forms an endonuclease.
  • This complex cleaves branched DNA structures that arise during stalled DNA replication.

Purpose of the Study:

  • To identify and characterize mouse Eme1.
  • To investigate the function of mammalian Eme1 in DNA repair and genome stability.

Main Methods:

  • Identified mouse Eme1 and confirmed its interaction with Mus81.
  • Assessed the cleavage preference of the Eme1-Mus81 complex in vitro.
  • Analyzed the sensitivity of Eme1-/- embryonic stem (ES) cells to various DNA damaging agents.
  • Evaluated the role of Eme1 in homologous recombination and sister chromatid exchange (SCE).

Main Results:

  • The mouse Eme1-Mus81 complex preferentially cleaves 3'-flap structures and replication forks.
  • Eme1-/- ES cells exhibit hypersensitivity to mitomycin C and cisplatin, but not to ionizing radiation, UV radiation, or hydroxyurea.
  • Eme1 is not essential for resolving DNA intermediates in homologous recombination.
  • Eme1 deficiency leads to spontaneous genomic instability and increased SCE following DNA damage.

Conclusions:

  • Mammalian Eme1 plays a critical role in DNA repair pathways.
  • Eme1 is essential for maintaining genome integrity, particularly in response to specific DNA damaging agents.

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