Histone variant Htz1 promotes histone H3 acetylation to enhance nucleotide excision repair in Htz1 nucleosomes.

摘要

Nucleotide excision repair (NER) is critical for maintaining genome integrity. How chromatin dynamics are regulated to facilitate this process in chromatin is still under exploration. We show here that a histone H2A variant, Htz1 (H2A.Z), in nucleosomes has a positive function in promoting efficient NER in yeast. Htz1 inherently enhances the occupancy of the histone acetyltransferase Gcn5 on chromatin to promote histone H3 acetylation after UV irradiation. Consequently, this results in an increased binding of a NER protein, Rad14, to damaged DNA. Cells without Htz1 show increased UV sensitivity and defective removal of UV-induced DNA damage in the Htz1-bearing nucleosomes at the repressed MFA2 promoter, but not in the HMRa locus where Htz1 is normally absent. Thus, the effect of Htz1 on NER is specifically relevant to its presence in chromatin within a damaged region. The chromatin accessibility to micrococcal nuclease in the MFA2 promoter is unaffected by HTZ1 deletion. Acetylation on previously identified lysines of Htz1 plays little role in NER or cell survival after UV. In summary, we have identified a novel aspect of chromatin that regulates efficient NER, and we provide a model for how Htz1 influences NER in Htz1 nucleosomes.Registry Number/Name of Substance 0 (Chromatin). 0 (Histones). 0 (Htz1 protein, S cerevisiae). 0 (Lipoproteins). 0 (MFA2 protein, S cerevisiae). 0 (Nucleosomes). 0 (Pheromones). 0 (Pyrimidine Dimers). 0 (RAD14 protein, S cerevisiae). 0 (Saccharomyces cerevisiae Proteins). EC 2-3-1-48 (GCN5 protein, S cerevisiae). EC 2-3-1-48 (Histone Acetyltransferases). EC 3-6-1 (Adenosine Triphosphatases). EC 3-6-1-3 (Swr1 protein, S cerevisiae). EC 6-5-1 (DNA Repair Enzymes).