ArticlePLoS genetics2011
A novel checkpoint and RPA inhibitory pathway regulated by Rif1.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 50 citations in OpenAlex.
- A CDK-Dependent Phosphorylation of a Novel Domain of Rif1 Regulates its Function during Telomere Damage and Other Types of Stress.Molecular and cellular biology · 2023Article
- Identification and characterization of biomarkers and their functions for docetaxel-resistant prostate cancer cells.Oncology letters · 2019Article
- Both a Unique Motif at the C Terminus and an N-Terminal HEAT Repeat Contribute to G-Quadruplex Binding and Origin Regulation by the Rif1 Protein.Molecular and cellular biology · 2019Article
- The Protective Role of Dormant Origins in Response to Replicative Stress.International journal of molecular sciences · 2018Review
- Shepherding DNA ends: Rif1 protects telomeres and chromosome breaks.Microbial cell (Graz, Austria) · 2018Review
- Rif1 phosphorylation site analysis in telomere length regulation and the response to damaged telomeres.DNA repair · 2018Article
- Oligomer formation and G-quadruplex binding by purified murine Rif1 protein, a key organizer of higher-order chromatin architecture.The Journal of biological chemistry · 2018Article
- Rif1 maintains telomeres and mediates DNA repair by encasing DNA ends.Nature structural & molecular biology · 2017Article
- Regulation of telomere metabolism by the RNA processing protein Xrn1.Nucleic acids research · 2017Article
- Fission yeast Stn1 is crucial for semi-conservative replication at telomeres and subtelomeres.Nucleic acids research · 2017Article
- Impaired 53BP1/RIF1 DSB mediated end-protection stimulates CtIP-dependent end resection and switches the repair to PARP1-dependent end joining in G1.Oncotarget · 2016Article
- Rif1 Regulates the Fate of DNA Entanglements during Mitosis.Cell reports · 2016Article
- Article
- Rif1: A Conserved Regulator of DNA Replication and Repair Hijacked by Telomeres in Yeasts.Frontiers in genetics · 2016Article
- Managing Single-Stranded DNA during Replication Stress in Fission Yeast.Biomolecules · 2015Review
- Drosophila Rif1 is an essential gene and controls late developmental events by direct interaction with PP1-87B.Scientific reports · 2015Article
- A tight control of Rif1 by Oct4 and Smad3 is critical for mouse embryonic stem cell stability.Cell death & disease · 2015Article
- Rad59-facilitated acquisition of Y' elements by short telomeres delays the onset of senescence.PLoS genetics · 2014Article
- At short telomeres Tel1 directs early replication and phosphorylates Rif1.PLoS genetics · 2014Article
- Saccharomyces cerevisiae Rif1 cooperates with MRX-Sae2 in promoting DNA-end resection.EMBO reports · 2014Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Cells accumulate single-stranded DNA (ssDNA) when telomere capping, DNA replication, or DNA repair is impeded. This accumulation leads to cell cycle arrest through activating the DNA-damage checkpoints involved in cancer protection. Hence, ssDNA accumulation could be an anti-cancer mechanism. However, ssDNA has to accumulate above a certain threshold to activate checkpoints. What determines this checkpoint-activation threshold is an important, yet unanswered question. Here we identify Rif1 (Rap1-Interacting Factor 1) as a threshold-setter. Following telomere uncapping, we show that budding yeast Rif1 has unprecedented effects for a protein, inhibiting the recruitment of checkpoint proteins and RPA (Replication Protein A) to damaged chromosome regions, without significantly affecting the accumulation of ssDNA at those regions. Using chromatin immuno-precipitation, we provide evidence that Rif1 acts as a molecular "band-aid" for ssDNA lesions, associating with DNA damage independently of Rap1. In consequence, small or incipient lesions are protected from RPA and checkpoint proteins. When longer stretches of ssDNA are generated, they extend beyond the junction-proximal Rif1-protected regions. In consequence, the damage is detected and checkpoint signals are fired, resulting in cell cycle arrest. However, increased Rif1 expression raises the checkpoint-activation threshold to the point it simulates a checkpoint knockout and can also terminate a checkpoint arrest, despite persistent telomere deficiency. Our work has important implications for understanding the checkpoint and RPA-dependent DNA-damage responses in eukaryotic cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.