Distinct roles of XRCC1 in genome integrity in Xenopus egg extracts

Biochem J. 2019 Dec 23;476(24):3791-3804. doi: 10.1042/BCJ20190798.

Abstract

Oxidative DNA damage represents one of the most abundant DNA lesions. It remains unclear how DNA repair and DNA damage response (DDR) pathways are co-ordinated and regulated following oxidative stress. While XRCC1 has been implicated in DNA repair, it remains unknown how exactly oxidative DNA damage is repaired and sensed by XRCC1. In this communication, we have demonstrated evidence that XRCC1 is dispensable for ATR-Chk1 DDR pathway following oxidative stress in Xenopus egg extracts. Whereas APE2 is essential for SSB repair, XRCC1 is not required for the repair of defined SSB and gapped plasmids with a 5'-OH or 5'-P terminus, suggesting that XRCC1 and APE2 may contribute to SSB repair via different mechanisms. Neither Polymerase beta nor Polymerase alpha is important for the repair of defined SSB structure. Nonetheless, XRCC1 is important for the repair of DNA damage following oxidative stress. Our observations suggest distinct roles of XRCC1 for genome integrity in oxidative stress in Xenopus egg extracts.

Keywords: APE2; ATR-Chk1; Pol beta; SSB repair; XRCC1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Extracts / chemistry*
  • Chromatin
  • DNA Damage
  • DNA Repair
  • Gene Expression Regulation
  • Genome*
  • Male
  • Ovum / chemistry
  • Ovum / metabolism*
  • Oxidative Stress
  • Plasmids
  • Spermatozoa
  • X-ray Repair Cross Complementing Protein 1 / chemistry
  • X-ray Repair Cross Complementing Protein 1 / genetics
  • X-ray Repair Cross Complementing Protein 1 / metabolism*
  • Xenopus / genetics
  • Xenopus / metabolism*

Substances

  • Cell Extracts
  • Chromatin
  • X-ray Repair Cross Complementing Protein 1