YY1 is involved in homologous recombination inhibition at guanine quadruplex sites in human cells

Abstract Homologous recombination (HR) is a key process for repairing DNA double strand breaks and for promoting genetic diversity. However, HR occurs unevenly across the genome, and certain genomic features can influence its activity. One such feature is the presence of guanine quadruplexes (G4s),...

Full description

Saved in:
Bibliographic Details
Published in:Nucleic acids research 2024-07, Vol.52 (13), p.7401-7413
Main Authors: Cui, Xinyu, Zhang, Chengwen, Fu, Chunqing, Hu, Jinglei, Li, Tengjiao, Li, Lin
Format: Article
Language:English
Subjects:
Chemical Biology and Nucleic Acid Chemistry
Chromatin - genetics
Chromatin - metabolism
DNA Breaks, Double-Stranded
G-Quadruplexes
Genomic Instability - genetics
Homologous Recombination - genetics
Humans
Rad51 Recombinase - genetics
Rad51 Recombinase - metabolism
RecQ Helicases - genetics
RecQ Helicases - metabolism
Sister Chromatid Exchange - genetics
YY1 Transcription Factor - genetics
YY1 Transcription Factor - metabolism
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Homologous recombination (HR) is a key process for repairing DNA double strand breaks and for promoting genetic diversity. However, HR occurs unevenly across the genome, and certain genomic features can influence its activity. One such feature is the presence of guanine quadruplexes (G4s), stable secondary structures widely distributed throughout the genome. These G4s play essential roles in gene transcription and genome stability regulation. Especially, elevated G4 levels in cells deficient in the Bloom syndrome helicase (BLM) significantly enhance HR at G4 sites, potentially threatening genome stability. Here, we investigated the role of G4-binding protein Yin Yang-1 (YY1) in modulating HR at G4 sites in human cells. Our results show that YY1’s binding to G4 structures suppresses sister chromatid exchange after BLM knockdown, and YY1’s chromatin occupancy negatively correlates with the overall HR rate observed across the genome. By limiting RAD51 homolog 1 (RAD51) access, YY1 preferentially binds to essential genomic regions, shielding them from excessive HR. Our findings unveil a novel role of YY1–G4 interaction, revealing novel insights into cellular mechanisms involved in HR regulation. Graphical Abstract Graphical Abstract
ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/gkae502