SUMMARY PARAGRAPH for RTT109
Rtt109p is a histone acetyltransferase that associates with transcriptionally active genes and is required for proper acetylation of histone H3 at lysine 56 (H3K56), which occurs during both the premeiotic and mitotic S phase, and persists throughout DNA damage repair (8). Rtt109p directly catalyzes the H3K56 acetylation in a manner that is stimulated by histone chaperone Asf1p, which governs the substrate specificity of Rtt109p. Rtt109p also autoacetylates and can weakly acetylate Asf1p, but not histone H4 (3). Acetylation of H3K56 has been implicated in regulation of replication since H3K56 is transiently acetylated during S phase (3). This H3K56 acetylation plays a critical role in conferring resistance to replication stress, and is critical for cell survival in the presence of DNA damage during S phase (3).
Specific mutations in Rtt109p (D89A, D89N, and DD287-288AA) result in loss of H3K56 acetylation. D89 is absolutely essential for H3K56 acetylation, whereas DD287-288 are not essential but contribute (3). The rtt109 aspartate mutants listed above, as well as rtt109 null mutants, which lack H3K56 acetylation, exhibit slow growth, and are hypersensitive to agents that generate replication stress (methyl methanesulfonate, hydroxyurea, campothecin) and to phleomycin, but not to acute ionizing radiation treatment, similar to that of asf1 null and H3K56Q mutants (8, 3). Further, RTT109 deletion leads to an increased rate of gross chromosomal rearrangements as well as a hyperrecombination phenotype similar to that exhibited by an sgs1 null mutant (2). rtt109 null mutants exhibit synthetic genetic interactions with mutations in POL30 (PCNA), POL1 (DNA polymerase alpha), ORC2, and CDC45, all of which are involved in DNA replication (3).
RTT109 was originally identified in a genetic screen for regulators of transposition of the retrotransposon Ty1 (1). Homologs of RTT109 are present in Schizosaccharomyces pombe, Eremothecium gossypii, Candida glabrata, C. albicans, and Kluyveromyces lactis.
Last updated: 2007-03-13