Abstract
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.
Highlights
The eukaryotic genome is packaged with histones and non-histone proteins to form chromatin
The gcn5D mutant is moderately sensitive to UV, and Gcn5 controls UVinduced histone H3 acetylation in the MFA2 promoter, which is required for efficient repair of cyclobutane pyrimidine dimers (CPDs) via Nucleotide excision repair (NER) [40,53]
Our previous studies, using the S. cerevisiae MFA2 gene as an example, revealed that histone H3 acetylation and chromatin remodelling are activated after UV irradiation, and both events are required for NER to efficiently process UV-induced CPDs in chromatin [40]
Summary
The eukaryotic genome is packaged with histones and non-histone proteins to form chromatin. This characteristic genome organization in eukaryotes makes chromatin the primary platform for almost all DNA-based events, including replication, transcription and DNA repair [1,2,3]. In addition to post-translational histone modifications [4] and ATP-dependent chromatin remodelling [5], incorporation of histone variants into nucleosomes [6,7] is another means by which cells regulate chromatin dynamics in response to internal and environmental cues. Htz is incorporated into the nucleosomes in the form of a Htz1–H2B dimer by the ATP-dependent SWR complex to replace H2A–H2B, and the incorporation is independent of DNA replication [10,11,12,13]
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