@article{62d66f784a574cd7bda181b9e9c45b32,
title = "The role of rif1 in telomere length regulation is separable from its role in origin firing",
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.",
keywords = "Dormant Origin, Origin activation, Rif1, Telomere length",
author = "Shubin, {Calla B.} and Greider, {Carol W.}",
note = "Funding Information: Dr. Brendan Cormack, Dr. Rebecca Keener, Samantha Sholes, Carla Connelly, and Margaret Strong for critical reading of the manuscript. This work was supported by the Bloomberg Distinguished Professorship (to C.W.G.), NSF GRFP DGE-1746891 (to C.B.S.), and NIGMS T32 GM007445 (to the BCMB graduate training program). Funding Information: We would like to acknowledge Dr. David Mohr and the Hopkins Genetics Resource Core Facility and High Throughput Sequencing Center for preparing and sequencing Illumina genomic DNA libraries. We thank Sarah Wheelan and Anuj Gupta from the SKCCC Experimental and Computational Genomics Core (NIH P30 CA006973) for advice and assistance in bioinformatics analysis of the copy number seq experiments. We would like to thank Drs. John Diffley and Anne Donaldson for strains and Dr. James Haber for the Cas9 plasmid and protocol. We would like to thank Kathryn Carson at the Johns Hopkins Biostatistics Center for statistics consultation. We would like to thank Drs. Thomas Kelly and Brendan Cormack for many helpful discussions about experimental design and data analysis. Finally, we would like to thank Dr. Thomas Kelly, Dr. Brendan Cormack, Dr. Rebecca Keener, Samantha Sholes, Carla Connelly, and Margaret Strong for critical reading of the manuscript. This work was supported by the Bloomberg Distinguished Professorship (to C.W.G.), NSF GRFP DGE-1746891 (to C.B.S.), and NIGMS T32 GM007445 (to the BCMB graduate training program). Publisher Copyright: {\textcopyright} 2020, eLife Sciences Publications Ltd. All rights reserved.",
year = "2020",
month = jun,
doi = "10.7554/eLife.58066",
language = "English (US)",
volume = "9",
pages = "1--40",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}