SCIENCE@home

APE1 is a master regulator of the ATR-/ATM-mediated DNA damage response.

Haichao Zhao,Christine Richardson,Ian Marriott,In Hong Yang,Shan Yan

Published 2024 in DNA Repair

ABSTRACT

To maintain genomic integrity, cells have evolved several conserved DNA damage response (DDR) pathways in response to DNA damage and stress conditions. Apurinic/apyrimidinic endonuclease 1 (APE1) exhibits AP endonuclease, 3'-5' exonuclease, 3'-phosphodiesterase, and 3'-exoribonuclease activities and plays critical roles in the DNA repair and redox regulation of transcription. However, it remains unclear whether and how APE1 is involved in DDR pathways. In this perspective, we first updated our knowledge of APE1's functional domains and its nuclease activities and their specific associated substrates. We then summarized the newly discovered roles and mechanisms of action of APE1 in the global and nucleolar ATR-mediated DDR pathway. While the ATM-mediated DDR is well known to be activated by DNA double-strand breaks and oxidative stress, here we provided new perspectives as to how ATM DDR signaling is activated by indirect single-strand breaks (SSBs) resulting from genotoxic stress and defined SSB structures, and discuss how ATM kinase is directly activated and regulated by its activator, APE1. Together, accumulating body of new evidence supports the notion that APE1 is a master regulator protein of the ATR- and ATM-mediated DDR pathways. These new findings of APE1 in DDR signaling provide previously uncharacterized but critical functions and regulations of APE1 in genome integrity.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-100 of 130 references · Page 1 of 2

12
Next

CITED BY

Showing 1-6 of 6 citing papers · Page 1 of 1