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Biomedical subjects

Anne C Harvey

Publications and source records attributed to Anne C Harvey.

2 recordsLinked to original sources

Saccharomyces cerevisiae histone H2A Ser122 facilitates DNA repair.

DNA repair takes place in the context of chromatin. Recently, it has become apparent that proteins that make up and modulate chromatin structure are involved in the detection and repair of DNA lesions. We previously demonstrated that Ser129 in the carboxyl-terminal tail of yeast histone H2A is important for double-strand-break responses. By undertaking a systematic site-directed mutagenesis approach, we identified another histone H2A serine residue (Ser122) that is important for survival in the presence of DNA-damaging agents. We show that mutation of this residue does not affect DNA damage-dependent Rad53 phosphorylation or G(2)/M checkpoint responses. Interestingly, we find that yeast lacking H2A S122 are defective in their ability to sporulate. Finally, we demonstrate that H2A S122 provides a function distinct from that of H2A S129. These data demonstrate a role for H2A S122 in facilitating survival in the presence of DNA damage and suggest a potential role in mediating homologous recombination. The distinct roles of H2A S122 and S129 in mediating these responses suggest that chromatin components can provide specialized functions for distinct DNA repair and survival mechanisms and point toward the possibility of a complex DNA damage responsive histone code.

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What functions do linker histones provide?

Linker histones have long been known to facilitate chromatin condensation in vitro. For many years, this activity led to speculation that these proteins function as global repressors of transcription. However, work from numerous systems has demonstrated that this is not the case, and that linker histones appear to affect only the transcription of a small subset of genes, and, in fact, act to activate as well as repress transcription. Furthermore, there is evidence that suggests that linker histones are not required for mitotic condensation. In this review, we focus on studies of biological functions of linker histones primarily performed in unicellular eukaryotes. We highlight recent developments pointing towards linker histone involvement in DNA repair and ageing, which raise the possibility that the biological functions of linker histones are more varied than previously imagined.

Animals↗