Telomere-to-mitochondria signalling by ZBP1 mediates replicative crisis

Abstract Cancers arise through the accumulation of genetic and epigenetic alterations that enable cells to evade telomere-based proliferative barriers and achieve immortality. One such barrier is replicative crisis—an autophagy-dependent program that eliminates checkpoint-deficient cells with unstable telomeres and other cancer-relevant chromosomal aberrations 1,2 . However, little is known about the molecular events that regulate the onset of this important tumour-suppressive barrier. Here we identified the innate immune sensor Z-DNA binding protein 1 (ZBP1) as a regulator of the crisis program. A crisis-associated isoform of ZBP1 is induced by the cGAS–STING DNA-sensing pathway, but reaches full activation…

• NS
  National Science Foundation
• AH
  American Heart Association

  Award: 19PABHI34610000
• SW
  Samuel Waxman Cancer Research Foundation
• GF
  Glenn Foundation for Medical Research
• EM
  European Molecular Biology Organization

  Award: ALTF 668-2019
• HS
  Highland Street Foundation
• SN
  Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
• NI
  National Institutes of Health

  Awards: RO1CA234047, RO1CA227934, AG064049, R01AR069876, RO1CA228211, P30CA014195
• NI
  National Institute on Aging

  Awards: AG068635, AG064049
• NC
  National Cancer Institute

  Awards: RO1CA234047, P30CA014195, RO1CA227934