Telomere end structure serves to protect chromosome ends from
degradation and end-to-end fusions, and to provide the substrate for the
telomere replication enzyme, telomerase. In S. cerevisiae ,
CDC13 is required for both of these functions. To uncover
additional genes required for telomere end-protection and/or
replication, we performed a screen for mutations that were required in
parallel with CDC13 . Surprisingly, mutations were recovered in
the Ku70/Ku80 heterodimer and the Mre11/Rad50/Xrs2 complex, both of
which are required for double strand break (DSB) repair via the
nonhomologous end-joining pathway. We have shown that Ku, previously
shown to bind double strand ends in vitro , plays a third role at
the telomere, required in parallel with telomerase and Cdc13p. We
propose that Ku and Cdc13p function as terminus-binding factors,
contributing non-overlapping roles in telomere end-protection. In
contrast, the Mre11/Rad50/Xrs2 complex is required for telomerase-mediated telomere replication, possibly via processing DNA ends in
preparation for telomerase activity. We are currently asking whether the
Mre11/Rad50/Xrs2 complex interacts with either the telomere or
telomerase, and whether chromosome end structure is altered in strains
mutant in this complex. In addition, a screen for Ku and
Mre11/Rad50/Xrs2 separation-of-function mutants is being performed to
address whether these repair proteins have differential roles at the
telomere versus at DSBs.
Return to YGM 1998 Abstract Index