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PMID:17267293

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Citation

Bostelman, LJ, Keller, AM, Albrecht, AM, Arat, A and Thompson, JS (2007) Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae. DNA Repair (Amst.) 6:383-95

Abstract

Various proteins have been found to play roles in both the repair of UV damaged DNA and heterochromatin-mediated silencing in the yeast Saccharomyces cerevisiae. In particular, factors that are involved in the methylation of lysine-79 of histone H3 by Dot1p have been implicated in both processes, suggesting a bipartite function for this modification. We find that a dot1 null mutation and a histone H3 point mutation at lysine-79 cause increased sensitivity to UV radiation, suggesting that lysine-79 methylation is important for efficient repair of UV damage. Epistasis analysis between dot1 and various UV repair genes indicates that lysine-79 methylation plays overlapping roles within the nucleotide excision, post-replication and recombination repair pathways, as well as RAD9-mediated checkpoint function. In contrast, epistasis analysis with the H3 lysine-79 point mutation indicates that the lysine-to-glutamic acid substitution exerts specific effects within the nucleotide excision repair and post-replication repair pathways, suggesting that this allele only disrupts a subset of the functions of lysine-79 methylation. The overall results indicate the existence of distinct and separable roles of histone H3 lysine-79 methylation in the response to UV damage, potentially serving to coordinate the various repair processes.

Links

PubMed Online version:10.1016/j.dnarep.2006.12.010

Keywords

Adenosine Triphosphatases/metabolism; Cell Cycle Proteins/metabolism; DNA/chemistry; DNA/metabolism; DNA Damage; DNA Helicases; DNA Repair; DNA Replication/physiology; Dose-Response Relationship, Radiation; Histone-Lysine N-Methyltransferase/metabolism; Histones/metabolism; Lysine/metabolism; Methylation; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Radiation, Ionizing; Recombination, Genetic/physiology; Saccharomyces cerevisiae/enzymology; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae/radiation effects; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Ultraviolet Rays

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