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Shepherding DNA ends: Rif1 protects telomeres and chromosome breaks
Cells have evolved conserved mechanisms to protect DNA ends, such as those at the termini of linear chromosomes, or those at DNA double-strand breaks (DSBs). In eukaryotes, DNA ends at chromosomal termini are packaged into proteinaceous structures called telomeres. Telomeres protect chromosome ends...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Shared Science Publishers OG
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035837/ https://www.ncbi.nlm.nih.gov/pubmed/29992129 http://dx.doi.org/10.15698/mic2018.07.639 |
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author | Fontana, Gabriele A. Reinert, Julia K. Thomä, Nicolas H. Rass, Ulrich |
author_facet | Fontana, Gabriele A. Reinert, Julia K. Thomä, Nicolas H. Rass, Ulrich |
author_sort | Fontana, Gabriele A. |
collection | PubMed |
description | Cells have evolved conserved mechanisms to protect DNA ends, such as those at the termini of linear chromosomes, or those at DNA double-strand breaks (DSBs). In eukaryotes, DNA ends at chromosomal termini are packaged into proteinaceous structures called telomeres. Telomeres protect chromosome ends from erosion, inadvertent activation of the cellular DNA damage response (DDR), and telomere fusion. In contrast, cells must respond to damage-induced DNA ends at DSBs by harnessing the DDR to restore chromosome integrity, avoiding genome instability and disease. Intriguingly, Rif1 (Rap1-interacting factor 1) has been implicated in telomere homeostasis as well as DSB repair. The protein was first identified in Saccharomyces cerevisiae as being part of the proteinaceous telosome. In mammals, RIF1 is not associated with intact telomeres, but was found at chromosome breaks, where RIF1 has emerged as a key mediator of pathway choice between the two evolutionary conserved DSB repair pathways of non-homologous end-joining (NHEJ) and homologous recombination (HR). While this functional dichotomy has long been a puzzle, recent findings link yeast Rif1 not only to telomeres, but also to DSB repair, and mechanistic parallels likely exist. In this review, we will provide an overview of the actions of Rif1 at DNA ends and explore how exclusion of end-processing factors might be the underlying principle allowing Rif1 to fulfill diverse biological roles at telomeres and chromosome breaks. |
format | Online Article Text |
id | pubmed-6035837 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Shared Science Publishers OG |
record_format | MEDLINE/PubMed |
spelling | pubmed-60358372018-07-10 Shepherding DNA ends: Rif1 protects telomeres and chromosome breaks Fontana, Gabriele A. Reinert, Julia K. Thomä, Nicolas H. Rass, Ulrich Microb Cell Microbiology Cells have evolved conserved mechanisms to protect DNA ends, such as those at the termini of linear chromosomes, or those at DNA double-strand breaks (DSBs). In eukaryotes, DNA ends at chromosomal termini are packaged into proteinaceous structures called telomeres. Telomeres protect chromosome ends from erosion, inadvertent activation of the cellular DNA damage response (DDR), and telomere fusion. In contrast, cells must respond to damage-induced DNA ends at DSBs by harnessing the DDR to restore chromosome integrity, avoiding genome instability and disease. Intriguingly, Rif1 (Rap1-interacting factor 1) has been implicated in telomere homeostasis as well as DSB repair. The protein was first identified in Saccharomyces cerevisiae as being part of the proteinaceous telosome. In mammals, RIF1 is not associated with intact telomeres, but was found at chromosome breaks, where RIF1 has emerged as a key mediator of pathway choice between the two evolutionary conserved DSB repair pathways of non-homologous end-joining (NHEJ) and homologous recombination (HR). While this functional dichotomy has long been a puzzle, recent findings link yeast Rif1 not only to telomeres, but also to DSB repair, and mechanistic parallels likely exist. In this review, we will provide an overview of the actions of Rif1 at DNA ends and explore how exclusion of end-processing factors might be the underlying principle allowing Rif1 to fulfill diverse biological roles at telomeres and chromosome breaks. Shared Science Publishers OG 2018-05-17 /pmc/articles/PMC6035837/ /pubmed/29992129 http://dx.doi.org/10.15698/mic2018.07.639 Text en https://creativecommons.org/licenses/by/4.0/ This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged. |
spellingShingle | Microbiology Fontana, Gabriele A. Reinert, Julia K. Thomä, Nicolas H. Rass, Ulrich Shepherding DNA ends: Rif1 protects telomeres and chromosome breaks |
title | Shepherding DNA ends: Rif1 protects telomeres and chromosome breaks |
title_full | Shepherding DNA ends: Rif1 protects telomeres and chromosome breaks |
title_fullStr | Shepherding DNA ends: Rif1 protects telomeres and chromosome breaks |
title_full_unstemmed | Shepherding DNA ends: Rif1 protects telomeres and chromosome breaks |
title_short | Shepherding DNA ends: Rif1 protects telomeres and chromosome breaks |
title_sort | shepherding dna ends: rif1 protects telomeres and chromosome breaks |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035837/ https://www.ncbi.nlm.nih.gov/pubmed/29992129 http://dx.doi.org/10.15698/mic2018.07.639 |
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