title: Deacetylase Rpd3 facilitates checkpoint adaptation by preventing Rad53 overactivation.
abstract: The DNA damage checkpoint is tightly controlled. After its activation, the checkpoint machinery is inactivated once lesions are repaired or undergoes adaptation if the DNA damage is unable to be repaired. Protein acetylation has been shown to play an important role in DNA damage checkpoint activation. However, the role of acetylation in checkpoint inactivation is unclear. Here we show that histone deacetylase Rpd3-mediated deacetylation of Rad53 plays an important role in checkpoint adaptation. Deletion of Rpd3 or inhibition of its activity impairs adaptation. RPD3 deletion also leads to a higher acetylation level and enhanced kinase activity of Rad53. Replacement of two major acetylation sites of Rad53 with arginine reduces its activity and further suppresses the adaptation defect of rpd3Δ cells, indicating that Rpd3 facilitates adaptation by preventing Rad53 overactivation. Similar to its role in adaptation, deletion of RPD3 or inhibition of its activity also suppressed checkpoint recovery. Altogether, our findings reveal an important role of Rpd3 in promoting checkpoint adaptation via deacetylation and inhibition of Rad53.
authors: The State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
authors: Ran
authors: R
authors: Tao
authors: Hua
authors: H
authors: Xue
authors: Jianping
authors: J
authors: Zhang
authors: Jieyuan
authors: J
authors: Liu
authors: Haiteng
authors: H
authors: Deng
authors: Ye-Guang
authors: YG
authors: Chen
mesh_terms: D000107:Acetylation; D000222:Adaptation, Physiological; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000378:metabolism*; D064447:Checkpoint Kinase 2 / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004789:Enzyme Activation; D017353:Gene Deletion; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D059767:Recombinational DNA Repair; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins; D014635:Valproic Acid; D064447:Checkpoint Kinase 2; C067022:RAD53 protein, S cerevisiae; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases
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