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

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...

Full description

Saved in:
Bibliographic Details
Published in:BioEssays 2024-05, Vol.46 (5), p.e2400011-e2400011
Main Authors: Petsalaki, Eleni, Zachos, George
Format: Article
Language:English
Subjects:
Abscission
Bridges
Cell division
Chromatin
Chromatin - metabolism
Cytokinesis
Cytokinesis - physiology
Damage localization
Deoxyribonucleic acid
DNA
DNA - metabolism
DNA damage
DNA topoisomerase
DNA Topoisomerases, Type II - metabolism
DNA-Binding Proteins - metabolism
Humans
INCENP protein
Localization
Poly-ADP-Ribose Binding Proteins - metabolism
Proteasomes
Proteins
Signal Transduction
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0265-9247
1521-1878
DOI:10.1002/bies.202400011