Activating the abscission checkpoint: Top2α senses chromatin bridges in cytokinesis: Top2α binds to DNA knots on chromatin bridges to activate the abscission checkpoint in human cells

Bioessays. 2024 May;46(5):e2400011. doi: 10.1002/bies.202400011. Epub 2024 Feb 25.

Abstract

How chromatin bridges are detected by the abscission checkpoint during mammalian cell division is unknown. Here, we discuss recent findings from our lab showing that the DNA topoisomerase IIα (Top2α) enzyme binds to catenated ("knotted") DNA next to the midbody and forms abortive Top2-DNA cleavage complexes (Top2ccs) on chromatin bridges. Top2ccs are then processed by the proteasome to promote localization of the DNA damage sensor protein Rad17 to Top2-generated double-strand DNA ends on DNA knots. In turn, Rad17 promotes local recruitment of the MRN protein complex and downstream ATM-Chk2-INCENP signaling to delay abscission and prevent chromatin bridge breakage in cytokinesis.

Keywords: Rad17; Topoisomerase II; abscission checkpoint; cell division; chromatin breakage; chromatin bridges; cytokinesis.

Publication types

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

MeSH terms

  • Chromatin* / metabolism
  • Cytokinesis* / physiology
  • DNA / metabolism
  • DNA Topoisomerases, Type II* / metabolism
  • DNA-Binding Proteins* / metabolism
  • Humans
  • Poly-ADP-Ribose Binding Proteins / metabolism
  • Signal Transduction

Substances

  • DNA Topoisomerases, Type II
  • Chromatin
  • DNA-Binding Proteins
  • Poly-ADP-Ribose Binding Proteins
  • TOP2A protein, human
  • DNA