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The ATR-WEE1 kinase module promotes SUPPRESSOR OF GAMMA RESPONSE 1 translation to activate replication stress

Hanchen Chen1,2,3,4,5, Ting Pan1,2,3,4,5, Xueao Zheng1,2,3,4,5

  • 1Hubei Hongshan Laboratory, Wuhan 430070, China.

The Plant Cell
|May 9, 2023
PubMed

Insights

DNA replication stress responses are regulated by ATR-WEE1 kinases controlling the translation of SOG1. This study reveals how inhibiting protein translation factors promotes SOG1 expression during stress.

Area of Science:

  • Plant molecular biology
  • Cellular stress response mechanisms
  • Genome stability

Background:

  • DNA replication stress is a critical threat to genome stability and a hallmark of human cancers.
  • The kinases ATR (ATM and RAD3-related) and WEE1 are key regulators of replication stress responses.
  • The role of translational control in these responses remains largely unexplored.

Purpose of the Study:

  • To investigate the role of translational control in DNA replication stress responses in Arabidopsis thaliana.
  • To elucidate the regulatory mechanism linking ATR-WEE1 kinases to the translation of the SOG1 transcription factor.

Main Methods:

  • Genetic screening to identify factors modulating replication stress sensitivity in atr and wee1 mutants.
  • Biochemical assays to determine the interaction and phosphorylation of GCN20 by WEE1.
  • Ribosome profiling to assess SOG1 translation efficiency under different genetic conditions.

Main Results:

  • Loss of GENERAL CONTROL NONDEREPRESSIBLE 20 (GCN20) or GCN1 suppressed replication stress hypersensitivity in atr or wee1 mutants.
  • WEE1 phosphorylates and promotes the degradation of GCN20, thereby inhibiting protein translation.
  • Loss of GCN20 enhanced SOG1 translation efficiency, while its overexpression reduced it.
  • SOG1 levels directly impacted resistance to replication stress in mutants.

Conclusions:

  • ATR-WEE1 kinases inhibit GCN20-GCN1 activity to promote SOG1 translation during replication stress.
  • This study establishes a novel link between translational control and DNA replication stress responses in plants.
  • Findings provide insights into maintaining genome stability under stress conditions.

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