Src activation by Chk1 promotes actin patch formation and prevents chromatin bridge breakage in cytokinesis

Dandoulaki, M., Petsalaki, E., Sumpton, D., Zanivan, S. and Zachos, G. (2018) Src activation by Chk1 promotes actin patch formation and prevents chromatin bridge breakage in cytokinesis. Journal of Cell Biology, 217(9), pp. 3071-3089. (doi:10.1083/jcb.201802102) (PMID:29954829)

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Abstract

In cytokinesis with chromatin bridges, cells delay abscission and retain actin patches at the intercellular canal to prevent chromosome breakage. In this study, we show that inhibition of Src, a protein-tyrosine kinase that regulates actin dynamics, or Chk1 kinase correlates with chromatin breakage and impaired formation of actin patches but not with abscission in the presence of chromatin bridges. Chk1 is required for optimal localization and complete activation of Src. Furthermore, Chk1 phosphorylates human Src at serine 51, and phosphorylated Src localizes to actin patches, the cell membrane, or the nucleus. Nonphosphorylatable mutation of S51 to alanine reduces Src catalytic activity and impairs formation of actin patches, whereas expression of a phosphomimicking Src-S51D protein rescues actin patches and prevents chromatin breakage in Chk1-deficient cells. We propose that Chk1 phosphorylates Src-S51 to fully induce Src kinase activity and that phosphorylated Src promotes formation of actin patches and stabilizes chromatin bridges. These results identify proteins that regulate formation of actin patches in cytokinesis.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Sumpton, Mr David and Zanivan, Dr Sara Rossana and Zachos, Dr George
Authors: Dandoulaki, M., Petsalaki, E., Sumpton, D., Zanivan, S., and Zachos, G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Journal of Cell Biology
Publisher:Rockefeller University Press
ISSN:0021-9525
ISSN (Online):1540-8140
Published Online:28 June 2018
Copyright Holders:Copyright © 2018 Dandoulaki et al.
First Published:First published in Journal of Cell Biology 217(9): 3071-3089
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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