RT Journal Article
T1 Physical proximity of chromatin to nuclear pores prevents harmful R loop accumulation contributing to maintain genome stability.
A1 García-Benítez, Francisco
A1 Gaillard, Hélène
A1 Aguilera, Andrés
K1 Mpl1/2
K1 R loop
K1 genome instability
K1 nuclear pores
K1 transcription
AB 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.
YR 2017
FD 2017-09-25
LK http://hdl.handle.net/10668/11645
UL http://hdl.handle.net/10668/11645
LA en
DS RISalud
RD Apr 12, 2025