Abstract
To examine the established link between DNA replication and telomere length, we tested whether firing of telomeric origins would cause telomere lengthening. We found that RIF1 mutants that block Protein Phosphatase 1 (PP1) binding activated telomeric origins but did not elongate telomeres. In a second approach, we found overexpression of ∆N-Dbf4 and Cdc7 increased DDK activity and activated telomeric origins, yet telomere length was unchanged. We tested a third mechanism to activate origins using the sld3-A mcm5-bob1 mutant that de-regulates the pre-replication complex, and again saw no change in telomere length. Finally, we tested whether mutations in RIF1 that cause telomere elongation would affect origin firing. We found that neither rif1-∆1322 nor rif1HOOK affected firing of telomeric origins. We conclude that telomeric origin firing does not cause telomere elongation, and the role of Rif1 in regulating origin firing is separable from its role in regulating telomere length.
Highlights
Telomeres are critical components of chromosome function
We found rif1∆ and our rif1-pp1bs mutant showed increased levels of Mcm4 phosphorylation compared to WT in both G1 and S phase, as other groups have shown (Figure 1A and Supplemental Figure 1C relating to Figure 1)
Having confirmed rif1∆ and our rif1-pp1bs increase Mcm4 phosphorylation, we examined their effects on both origin firing and telomere length
Summary
Telomeres are critical components of chromosome function. They consist of tandem repeats of simple G and T rich sequences at the ends of eukaryotic chromosomes. Telomere lengths differ between species, but, in all healthy cells, length is maintained within a defined length distribution (Greider, 1996). How this distribution of telomere lengths is established and maintained is not well understood. The maintenance of the length distribution is crucial, as short telomeres signal a DNA damage response that limits cell division (Hemann et al, 2001; Enomoto et al, 2002; d'Adda di Fagagna et al, 2003; IJpma and Greider, 2003). Understanding the molecular basis of telomere length maintenance has important implications for human disease
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