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doi:10.1534/genetics.106.057794
A more recent version of this article appeared on August 1, 2006.
REGULAR RESEARCH PAPERS |
The RAD6/BRE1 histone modification pathway in Saccharomyces confers radiation resistance through a RAD51-dependent process that is independent of RAD18
John C. Game 1*, Marsha S Williamson 1, Tatiana Spicakova 2 and Martin Brown 3
1 Lawrence Berkeley National Laboratory
2 Stanford University School of Medicine
3 Stanford University
* To whom correspondence should be addressed. E-mail: jcgame{at}lbl.gov.
Submitted on March 2, 2006
Revised on April 11, 2006
Accepted on 3 June 2006
We examine ionizing radiation (IR) sensitivity and epistasis relationships of several Saccharomyces mutants affecting post-translational modifications of histones H2B and H3. Mutants bre1
, lge1 and rtf1, defective in histone H2B lysine 123 ubiquitination, show IR sensitivity equivalent to that of the dot1 mutant we reported on earlier, consistent with published findings that Dot1p requires H2B K123 ubiquitination in order to fully methylate histone H3 K79. This implicates progressive K79 methylation rather than mono-methylation in IR resistance. The set2 mutant, defective in H3 K36 methylation, shows mild IR sensitivity whereas mutants that abolish H3 K4 methylation resemble wild-type. The dot1, bre1 and lge1 mutants show epistasis for IR sensitivity. The paf1 mutant, also reportedly defective in H2B K123 ubiquitination, confers no sensitivity. The rad6, rad51null, rad50 and rad9 mutations are epistatic to bre1 and dot1, but rad18 and rad5 show additivity with bre1, dot1 and each other. The bre1 rad18 double mutant resembles rad6 in sensitivity, thus the role of Rad6p in ubiquitinating H2B accounts for its extra sensitivity compared to rad18. We conclude that IR resistance conferred by BRE1 and DOT1 is mediated through homologous recombinational repair, not post-replication repair, and confirm findings of a G1 checkpoint role for the RAD6/BRE1/DOT1 pathway.
Key Words: BRE1 and RAD6, Cell Cycle checkpoints, DNA repair, Histone modifications, Ionizing Radiation
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