Please use this identifier to cite or link to this item:
Title: Physical proximity of chromatin to nuclear pores prevents harmful R loop accumulation contributing to maintain genome stability.
Authors: García-Benítez, Francisco
Gaillard, Hélène
Aguilera, Andrés
Keywords: Mpl1/2;R loop;genome instability;nuclear pores;transcription
metadata.dc.subject.mesh: Chromatin
Cytidine Deaminase
DNA Replication
DNA, Fungal
Genomic Instability
Nuclear Pore
Nuclear Proteins
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Transcription, Genetic
Issue Date: 25-Sep-2017
Abstract: During transcription, the mRNA may hybridize with DNA, forming an R loop, which can be physiological or pathological, constituting in this case a source of genomic instability. To understand the mechanism by which eukaryotic cells prevent harmful R loops, we used human activation-induced cytidine deaminase (AID) to identify genes preventing R loops. A screening of 400 Saccharomyces cerevisiae selected strains deleted in nuclear genes revealed that cells lacking the Mlp1/2 nuclear basket proteins show AID-dependent genomic instability and replication defects that were suppressed by RNase H1 overexpression. Importantly, DNA-RNA hybrids accumulated at transcribed genes in mlp1/2 mutants, indicating that Mlp1/2 prevents R loops. Consistent with the Mlp1/2 role in gene gating to nuclear pores, artificial tethering to the nuclear periphery of a transcribed locus suppressed R loops in mlp1∆ cells. The same occurred in THO-deficient hpr1∆ cells. We conclude that proximity of transcribed chromatin to the nuclear pore helps restrain pathological R loops.
metadata.dc.identifier.doi: 10.1073/pnas.1707845114
Appears in Collections:Producción 2020

Files in This Item:
There are no files associated with this item.

This item is protected by original copyright

Except where otherwise noted, Items on the Andalusian Health Repository site are licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives License.