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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. and Stratigi, K. and Siametis, A. and Goulielmaki, E. and Akalestou-Clocher, A. and Tsamardinos, I. and Topalis, P. and Austin, C. and Bouwman, B.A.M. and Crosetto, N. and 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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