A novel role for greatwall kinase in recovery from DNA damage

Aimin Peng, Tomomi M. Yamamoto, Michael L. Goldberg, James L. Maller

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Activation of the DNA damage response (DDR) is critical for genomic integrity and tumor suppression. The occurrence of DNA damage quickly evokes the DDR through ATM/ATR-dependent signal transduction, which promotes DNA repair and activates the checkpoint to halt cell cycle progression. The "turn off" process of the DDR upon satisfaction of DNA repair, also known as "checkpoint recovery", involves deactivation of DDR elements, but the mechanism is poorly understood. Greatwall kinase (Gwl) has been identified as a key element in the G2/M transition and helps maintain M phase through inhibition of PP 2A/B55δ, the principal phosphatase for Cdk-phosphorylated substrates. Here we show that Gwl also promotes recovery from DNA damage and is itself directly inhibited by the DNA damage response (DDR). In Xenopus egg extracts, immunodepletion of Gwl increased the DDR to damaged DNA, whereas addition of wild type, but not kinase dead Gwl, inhibited the DDR. The removal of damaged DNA from egg extracts leads to recovery from checkpoint arrest and entry into mitosis, a process impaired by Gwl depletion and enhanced by Gwl overexpression. Moreover, activation of Cdk1 after the removal of damaged DNA is regulated by Gwl. Collectively, these results defines Gwl as a new regulator of the DDR, which plays an important role in recovery from DNA damage.

Original languageEnglish (US)
Pages (from-to)4364-4369
Number of pages6
JournalCell Cycle
Volume9
Issue number21
DOIs
StatePublished - Nov 1 2010

Fingerprint

DNA Damage
Phosphotransferases
DNA Repair
Ovum
DNA
Response Elements
Xenopus
Phosphoric Monoester Hydrolases
Mitosis
Cell Division
Signal Transduction
Cell Cycle

Keywords

  • Checkpoint recovery
  • DNA damage
  • Greatwall

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Peng, A., Yamamoto, T. M., Goldberg, M. L., & Maller, J. L. (2010). A novel role for greatwall kinase in recovery from DNA damage. Cell Cycle, 9(21), 4364-4369. https://doi.org/10.4161/cc.9.21.13632

A novel role for greatwall kinase in recovery from DNA damage. / Peng, Aimin; Yamamoto, Tomomi M.; Goldberg, Michael L.; Maller, James L.

In: Cell Cycle, Vol. 9, No. 21, 01.11.2010, p. 4364-4369.

Research output: Contribution to journalArticle

Peng, A, Yamamoto, TM, Goldberg, ML & Maller, JL 2010, 'A novel role for greatwall kinase in recovery from DNA damage', Cell Cycle, vol. 9, no. 21, pp. 4364-4369. https://doi.org/10.4161/cc.9.21.13632
Peng, Aimin ; Yamamoto, Tomomi M. ; Goldberg, Michael L. ; Maller, James L. / A novel role for greatwall kinase in recovery from DNA damage. In: Cell Cycle. 2010 ; Vol. 9, No. 21. pp. 4364-4369.
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