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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...

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Autores principales: Fontana, Gabriele A., Reinert, Julia K., Thomä, Nicolas H., Rass, Ulrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Shared Science Publishers OG 2018
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.
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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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