Greatwall and polo-like kinase 1 coordinate to promote checkpoint recovery

Aimin Peng, Ling Wang, Laura A. Fisher

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Checkpoint recovery upon completion of DNA repair allows the cell to return to normal cell cycle progression and is thus a crucial process that determines cell fate after DNA damage. We previously studied this process in Xenopus egg extracts and established Greatwall (Gwl) as an important regulator. Here we show that preactivated Gwl kinase can promote checkpoint recovery independently of cyclin-dependent kinase 1 (Cdk1) or Plx1 (Xenopus polo-like kinase 1), whereas depletion of Gwl from extracts exhibits no synergy with that of Plx1 in delaying checkpoint recovery, suggesting a distinct but related relationship between Gwl and Plx1. In further revealing their functional relationship, we found mutual dependence for activation of Gwl and Plx1 during checkpoint recovery, as well as their direct association. We characterized the protein association in detail and recapitulated it in vitro with purified proteins, which suggests direct interaction. Interestingly, Gwl interaction with Plx1 and its phosphorylation by Plx1 both increase at the stage of checkpoint recovery. More importantly, Plx1-mediated phosphorylation renders Gwl more efficient in promoting checkpoint recovery, suggesting a functional involvement of such regulation in the recovery process. Finally, we report an indirect regulatory mechanism involving Aurora A that may account for Gwl-dependent regulation of Plx1 during checkpoint recovery. Our results thus reveal novel mechanisms underlying the involvement of Gwl in checkpoint recovery, in particular, its functional relationship with Plx1, a well characterized regulator of checkpoint recovery. Coordinated interplays between Plx1 and Gwl are required for reactivation of these kinases from the G2/M DNA damage checkpoint and efficient checkpoint recovery.

Original languageEnglish (US)
Pages (from-to)28996-29004
Number of pages9
JournalJournal of Biological Chemistry
Volume286
Issue number33
DOIs
StatePublished - Aug 19 2011

Fingerprint

DNA Damage
Phosphotransferases
Phosphorylation
CDC2 Protein Kinase
Recovery
Xenopus
DNA Repair
Ovum
Cell Cycle
Proteins
DNA
polo-like kinase 1
Association reactions
Repair
In Vitro Techniques
Xenopus Plk1 protein
Chemical activation
Cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Greatwall and polo-like kinase 1 coordinate to promote checkpoint recovery. / Peng, Aimin; Wang, Ling; Fisher, Laura A.

In: Journal of Biological Chemistry, Vol. 286, No. 33, 19.08.2011, p. 28996-29004.

Research output: Contribution to journalArticle

Peng, Aimin ; Wang, Ling ; Fisher, Laura A. / Greatwall and polo-like kinase 1 coordinate to promote checkpoint recovery. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 33. pp. 28996-29004.
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