Transformation/transcription domain-associated protein (TRRAP)-mediated regulation of Wee1.

ABSTRACT: The G2 DNA damage checkpoint inhibits Cdc2 and mitotic entry through the dual regulation of Wee1 and Cdc25 by the Chk1 effector kinase. Upregulation of Chk1 by mutation or overexpression bypasses the requirement for upstream regulators or DNA damage to promote a G2 cell cycle arrest. We screened in fission yeast for mutations that rendered cells resistant to overexpressed chk1(+). We identified a mutation in tra1, which encodes one of two homologs of transformation/transcription domain-associated protein (TRRAP), an ATM/R-related pseudokinase that scaffolds several histone acetyltransferase (HAT) complexes. Inhibition of histone deacetylases reverts the resistance to overexpressed chk1(+), suggesting this phenotype is due to a HAT activity, although expression of checkpoint and cell cycle

SUBMITTER: Calonge TM 

PROVIDER: S-EPMC2870978 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature