The Role of Rif1 in telomere length regulation is separable from its role in origin firing

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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 rif1_HOOK 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.

Data availability

Sequencing data have been deposited in NCBI BioProject/SRA PRJNA627739, Copy number sequencing in S. cerevisiae under SRA accession codes: SRR11601580, SRR11601579, SRR11601583, SRR11601584, SRR11601587, SRR11601586, SRR11601594, SRR11601592, SRR11601590, SRR11601589, SRR11601585, SRR11601591, SRR11601582, SRR11601593, SRR11601588, SRR11601581, SRR11601576, SRR11601577, SRR11601578, SRR11601575

The following data sets were generated

1. Shubin CB
2. Greider CW
(2020) Copy number sequencing in S. cerevisiae
NCBI BioProject/SRA, PRJNA627739.

https://www.ncbi.nlm.nih.gov/bioproject/PRJNA627739

Article and author information

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Calla B Shubin

Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-4618-2722
Carol W Greider

Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United States

For correspondence
cgreider@jhmi.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5494-8126

Funding

National Science Foundation (DGE-1746891)

Calla B Shubin

National Institute of General Medical Sciences (T32 GM007445)

Calla B Shubin

Bloomberg Distinguished Professorship

Carol W Greider

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.