Shepherding DNA ends: Rif1 protects telomeres and chromosome breaks

Fontana, Gabriele A, Reinert, Julia K, Thomä, Nicolas H and Rass, Ulrich (2018) Shepherding DNA ends: Rif1 protects telomeres and chromosome breaks. Microbial Cell, 5 (7). pp. 327-343. ISSN 2311-2638

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Abstract

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 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.

Item Type: Article
Keywords: Genome stability, DNA repair, DNA double-strand break repair pathway choice, telomere homeostasis
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Research Centres and Groups: Genome Damage and Stability Centre
Subjects: Q Science
Depositing User: Ulrich Rass
Date Deposited: 24 Sep 2018 11:28
Last Modified: 24 Sep 2018 11:28
URI: http://sro.sussex.ac.uk/id/eprint/78924

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