APE2 Zf-GRF facilitates 3′-5′ resection of DNA damage following oxidative stress Academic Article uri icon

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abstract

  • Significance Zf-GRF domains are found in more than 100 eukaryotic architectures, including key proteins modulating DNA damage response and transcription. We establish the apurinic/apyrimidinic endonuclease 2 (APE2) Zf-GRF domain as a prototypical member of the Zf-GRF class of nucleic acid-binding modules, and through structural analysis reveal that the APE2 protein is composed of a compacted three-stranded β-sheet and a CHCC Zn 2+ -binding site, harboring structure-specific ssDNA-binding activity. Notably, the ssDNA-binding region of APE2 Zf-GRF is required for the 3′-5′ end resection of oxidative DNA damage and activation of the ATR-Chk1 DNA damage response pathway following oxidative stress. This distinct regulatory mechanism of APE2 exonuclease activity by ssDNA binding via Zf-GRF may extend to other Zf-GRF–containing proteins.

authors

  • Wallace, Bret D
  • Berman, Zachary
  • Mueller, Geoffrey A
  • Lin, Yunfeng
  • Chang, Timothy
  • Andres, Sara
  • Wojtaszek, Jessica L
  • DeRose, Eugene F
  • Appel, C Denise
  • London, Robert E
  • Yan, Shan
  • Williams, R Scott

publication date

  • January 10, 2017