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.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Tao R,Xue H,Zhang J,Liu J,Deng H,Chen YGdoi
10.1128/MCB.00618-13subject
Has Abstractpub_date
2013-11-01 00:00:00pages
4212-24issue
21eissn
0270-7306issn
1098-5549pii
MCB.00618-13journal_volume
33pub_type
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