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

J Cell Biol. 2018 Sep 3;217(9):3071-3089. doi: 10.1083/jcb.201802102. Epub 2018 Jun 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins / metabolism
  • Aurora Kinase B / metabolism
  • Cell Line, Tumor
  • Checkpoint Kinase 1 / genetics
  • Checkpoint Kinase 1 / metabolism*
  • Chromatin / metabolism*
  • Chromosome Breakage*
  • Cytokinesis / physiology*
  • HeLa Cells
  • Humans
  • Phosphorylation
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Signal Transduction / genetics
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism*


  • Actins
  • Chromatin
  • RNA, Small Interfering
  • src-Family Kinases
  • AURKB protein, human
  • Aurora Kinase B
  • CHEK1 protein, human
  • Checkpoint Kinase 1