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Yeast Nucleolin Nsr1 Impedes Replication and Elevates Genome Instability at an Actively Transcribed Guanine-Rich G4-DNA Forming Sequence.
GENETICS ( IF 3.3 ) Pub Date : 2020-10-26 , DOI: 10.1534/genetics.120.303736 Shivani Singh 1 , Alexandra Berroyer 1, 2 , Minseon Kim 1, 2 , Nayun Kim 2, 3
GENETICS ( IF 3.3 ) Pub Date : 2020-10-26 , DOI: 10.1534/genetics.120.303736 Shivani Singh 1 , Alexandra Berroyer 1, 2 , Minseon Kim 1, 2 , Nayun Kim 2, 3
Affiliation
A significant increase in genome instability is associated with the conformational shift of a guanine-run-containing DNA strand into the four-stranded G-quadruplex (G4) DNA. The mechanism underlying the recombination and genome rearrangements following the formation of G4 DNA in vivo has been difficult to elucidate but has become better clarified by the identification and functional characterization of several key G4 DNA-binding proteins. Mammalian nucleolin NCL is a highly specific G4 DNA-binding protein with a well-defined role in the transcriptional regulation of genes with associated G4 DNA-forming sequence motifs at their promoters. The consequence of the in vivo interaction between G4 DNA and nucleolin in respect to the genome instability has not been previously investigated. We show here that the yeast nucleolin Nsr1 is enriched at a G4 DNA- forming sequence in vivo and is a major factor in inducing the genome instability associated with the co-transcriptionally formed G4 DNA in the yeast genome. We also show that Nsr1 results in impeding replication past such G4 DNA-forming sequence. The G4-associated genome instability and the G4 DNA-binding in vivo requires the arginine-glycine-glycine (RGG) repeats located at the C-terminus of the Nsr1 protein. Nsr1 with the deletion of RGG domain supports normal cell growth and is sufficient for its pre-rRNA processing function. However, the truncation of RGG domain of Nsr1 significantly weakens its interaction with G4 DNA in vivo and restores unhindered replication, overall resulting in a sharp reduction in the genome instability associated with guanine-rich G4 DNA-forming sequence. Our data suggest that the interaction between Nsr1 with the intact RGG repeats and G4 DNA impairs genome stability by precluding the access of G4-resolving proteins and impeding replication.
更新日期：2020-10-31
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