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APE1 senses DNA single-strand breaks for repair and signaling

Yunfeng Lin1, Jude Raj1, Jia Li1

  • 1Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.

Nucleic Acids Research
|December 13, 2019
PubMed

Insights

DNA single-strand breaks (SSBs) are repaired through a two-step process involving APE1 and APE2. This mechanism coordinates DNA damage response and repair, crucial for preventing diseases like cancer.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • DNA single-strand breaks (SSBs) are the most frequent DNA damage.
  • Unrepaired SSBs can lead to cancer and neurodegenerative diseases.
  • The coordination of SSB repair and signaling pathways is not fully understood.

Purpose of the Study:

  • To elucidate the coordinated regulation of SSB repair and signaling pathways.
  • To identify the key enzymes involved in SSB end resection.
  • To investigate the role of APE1 exonuclease activity in cancer etiology.

Main Methods:

  • Utilized Xenopus egg extract and in vitro reconstitution systems.
  • Investigated the roles of APE1, APE2, and PCNA in SSB repair.
  • Analyzed an APE1 exonuclease-deficient mutant from a cancer patient.

Main Results:

  • SSBs are initially sensed by APE1, initiating 3'-5' SSB end resection.
  • APE2 is recruited to continue the SSB end resection process.
  • APE1's exonuclease activity is essential for both SSB repair and signaling, with a deficient mutant linked to cancer.
  • APE1 interacts with APE2 and PCNA, though PCNA is not required for APE1's exonuclease function.

Conclusions:

  • A two-step APE1/APE2-mediated mechanism for SSB end resection couples DNA damage response with SSB repair.
  • APE1 exonuclease activity is critical for maintaining genomic stability and preventing cancer.
  • This study provides a comprehensive model for eukaryotic SSB repair coordination.

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