System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Epublish 6 citations

PubMed: 39112456 DOI: 10.1038/s41467-024-50836-6

Distinct regulation of ATM signaling by DNA single-strand breaks and APE1.

Nat Commun 15(1):6517

Authors: Haichao Zhao, Jia Li, Zhongsheng You, Howard D Lindsay, Shan Yan

Affiliations

  • Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC, 28223, USA.
  • Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Lancaster Medical School, Faculty of Health and Medicine, Lancaster University, Lancaster, LA1 4YQ, UK.
  • Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC, 28223, USA.
  • School of Data Science, University of North Carolina at Charlotte, Charlotte, NC, 28223, USA.
  • Center for Biomedical Engineering and Science, University of North Carolina at Charlotte, Charlotte, USA.

Abstract

In response to DNA double-strand breaks or oxidative stress, ATM-dependent DNA damage response (DDR) is activated to maintain genome integrity. However, it remains elusive whether and how DNA single-strand breaks (SSBs) activate ATM. Here, we provide direct evidence in Xenopus egg extracts that ATM-mediated DDR is activated by a defined SSB structure. Our mechanistic studies reveal that APE1 promotes the SSB-induced ATM DDR through APE1 exonuclease activity and ATM recruitment to SSB sites. APE1 protein can form oligomers to activate the ATM DDR in Xenopus egg extracts in the absence of DNA and can directly stimulate ATM kinase activity in vitro. Our findings reveal distinct mechanisms of the ATM-dependent DDR activation by SSBs in eukaryotic systems and identify APE1 as a direct activator of ATM kinase.

MeSH

Biological Science Disciplines, Ovum, Dna

Cited by