Histone acetylation, chromatin remodelling, transcription and nucleotide excision repair in S. cerevisiae: studies with two model genes.

ABSTRACT

We describe the technology and two model systems in yeast designed to study nucleotide excision repair (NER) in relation to transcription and chromatin modifications. We employed the MFA2 and MET16 genes as models. How transcription-coupled (TCR) and global genome repair (GGR) operate at the transcriptionally active and/or repressed S. cerevisiae MFA2 locus, and how this relates to nucleosome positioning are considered. We discuss the role of the Gcn5p histone acetyltransferase, also associated with MFA2's transcriptional activation, in facilitating efficient NER at the transcriptionally active and inactive genes. The effect of Gcn5p's absence in reducing NER was local and UV stimulates Gcn5p-mediated histone acetylation at the repressed MFA2 promoter. After UV irradiation Swi2p is partly responsible for facilitating access to restriction of DNA in the cores of the nucleosomes at the MFA2 promoter. The data suggest similarities between chromatin remodelling for NER and transcription, yet differences must exist to ensure this gene remains repressed in alpha cells during NER. For MET16, we consider experiments examining chromatin structure, transcription and repair in wild type and cbf1Delta cells under repressing or derepressing conditions. Cbf1p is a sequence specific DNA binding protein required for MET16 chromatin remodelling and transcription.