Open AccessRibosomal RNA gene repeats associate with the nuclear pore complex for maintenance after DNA damage
Author(s) -
Chihiro Horigome,
Eri Unozawa,
Takamasa Ooki,
Takehiko Kobayashi
Publication year - 2019
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1008103
Subject(s) - biology , genetics , dna repair , dna replication , gene , genome instability , ribosomal dna , dna damage , replisome , dna , microbiology and biotechnology , eukaryotic dna replication , phylogenetics
The ribosomal RNA genes (rDNA) comprise a highly repetitive gene cluster. The copy number of genes at this locus can readily change and is therefore one of the most unstable regions of the genome. DNA damage in rDNA occurs after binding of the replication fork blocking protein Fob1 in S phase, which triggers unequal sister chromatid recombination. However, the precise mechanisms by which such DNA double-strand breaks (DSBs) are repaired is not well understood. Here, we demonstrate that the conserved protein kinase Tel1 maintains rDNA stability after replication fork arrest. We show that rDNA associates with nuclear pores, which is dependent on DNA damage checkpoint kinases Mec1/Tel1 and replisome component Tof1. These findings suggest that rDNA-nuclear pore association is due to a replication fork block and subsequent DSB. Indeed, quantitative microscopy revealed that rDNA is relocated to the nuclear periphery upon induction of a DSB. Finally, rDNA stability was reduced in strains where this association with the nuclear envelope was prevented, which suggests its importance for avoiding improper recombination repair that could induce repeat instability.