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XPF interacts with TOP2B for R-loop processing and DNA looping on actively transcribed genes

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Item Type:Article
Title:XPF interacts with TOP2B for R-loop processing and DNA looping on actively transcribed genes
Creators Name:Chatzinikolaou, G., Stratigi, K., Siametis, A., Goulielmaki, E., Akalestou-Clocher, A., Tsamardinos, I., Topalis, P., Austin, C., Bouwman, B.A.M., Crosetto, N., Altmüller, J. and Garinis, G.A.
Abstract:Co-transcriptional RNA-DNA hybrids can not only cause DNA damage threatening genome integrity but also regulate gene activity in a mechanism that remains unclear. Here, we show that the nucleotide excision repair factor XPF interacts with the insulator binding protein CTCF and the cohesin subunits SMC1A and SMC3, leading to R-loop-dependent DNA looping upon transcription activation. To facilitate R-loop processing, XPF interacts and recruits with TOP2B on active gene promoters, leading to double-strand break accumulation and the activation of a DNA damage response. Abrogation of TOP2B leads to the diminished recruitment of XPF, CTCF, and the cohesin subunits to promoters of actively transcribed genes and R-loops and the concurrent impairment of CTCF-mediated DNA looping. Together, our findings disclose an essential role for XPF with TOP2B and the CTCF/cohesin complex in R-loop processing for transcription activation with important ramifications for DNA repair-deficient syndromes associated with transcription-associated DNA damage.
Keywords:CCCTC-Binding Factor, Chromatin, Chromosomes, DNA Repair, DNA-Binding Proteins, R-Loop Structures
Source:Science Advances
ISSN:2375-2548
Publisher:American Association for the Advancement of Science
Volume:9
Number:45
Page Range:eadi2095
Date:10 November 2023
Official Publication:https://doi.org/10.1126/sciadv.adi2095
PubMed:View item in PubMed

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