Interaction between Set1p and checkpoint protein Mec3p in DNA repair and telomere functions

The yeast protein Set1p, inactivation of which alleviates telomeric positio n effect (TPE), contains a conserved SET domain present in chromosomal prot eins involved in epigenetic control of transcription(1-2). Mec3p is require d for efficient DNA-damage-dependent checkpoints at G1/S, intra-S and G2/M (refs 3-7). We show here that the SET domain of Set1p interacts with Mec3p. Deletion of SET1 increases the viability of mec3 Delta mutants after DNA d amage (in a process that is mostly independent of Rad53p kinase, which has a central role in checkpoint control(8-9)) but does not significantly affec t cell-cycle progression. Deletion of MEC3 enhances TPE and attenuates the set1 Delta-induced silencing defect. Furthermore, restoration of TPE in a s et1 Delta mutant by overexpression of the isolated SET domain requires Mec3 p. Finally, deletion of MEC3 results in telomere elongation, whereas cells with deletions of both SET1 and MEC3 do not have elongated telomeres. Our f indings indicate that interactions between SET1 and MEC3 have a role in DNA repair and telomere function.