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Fluorescence-Based Detection of FEN1 Nuclease Activity and Screening of Small-Molecule Inhibitors
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Fluorescence-Based Detection of FEN1 Nuclease Activity and Screening of Small-Molecule Inhibitors

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Functional regulation of FEN1 nuclease and its link to cancer

Li Zheng1, Jia Jia, L David Finger

  • 1Institute of Cell Biology and Genetics, College of Life Sciences, Zhejiang University, Hangzhou, China.

Nucleic Acids Research
|October 9, 2010
PubMed

Insights

Flap endonuclease-1 (FEN1) is a versatile enzyme crucial for DNA repair and replication. Its multiple activities and interactions highlight its role in maintaining genome stability and its significance as a tumor suppressor.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • Flap endonuclease-1 (FEN1) is a key enzyme in the Rad2 nuclease family.
  • FEN1 exhibits FEN, 5'-exonuclease, and gap-endonuclease activities.
  • These activities enable FEN1's involvement in DNA replication, repair, and apoptosis.

Purpose of the Study:

  • To summarize the diverse roles of FEN1's nuclease activities in DNA metabolic pathways.
  • To discuss the regulation of FEN1 through protein interactions and post-translational modifications.
  • To review FEN1's biological significance as a tumor suppressor.

Main Methods:

  • Literature review of biochemical and genetic studies on FEN1.
  • Analysis of FEN1's interactions with over 30 proteins.
  • Examination of FEN1's post-translational modifications and their regulatory effects.

Main Results:

  • FEN1 participates in Okazaki fragment maturation, stalled replication fork rescue, telomere maintenance, base excision repair, and apoptotic DNA fragmentation.
  • FEN1 interacts with distinct protein groups, facilitating its recruitment to specific DNA metabolic complexes.
  • Protein interactions and post-translational modifications regulate FEN1 activity, localization, and interactions.

Conclusions:

  • FEN1's multiple nuclease activities are essential for various DNA metabolic processes.
  • FEN1 regulation involves intricate protein-protein interactions and post-translational modifications.
  • FEN1 functions as a tumor suppressor, with implications from human mutations and mouse models.

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