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| Item Type: | Article |
|---|---|
| Title: | XPF interacts with TOP2B for R-loop processing and DNA looping on actively transcribed genes |
| Creators: |
Chatzinikolaou, G.  ORCID: https://orcid.org/0000-0002-0868-0683, Stratigi, K. ORCID: https://orcid.org/0000-0001-7476-6410, Siametis, A. ORCID: https://orcid.org/0000-0003-0668-7563, Goulielmaki, E. ORCID: https://orcid.org/0000-0003-1651-3137, Akalestou-Clocher, A. ORCID: https://orcid.org/0000-0002-1267-6054, Tsamardinos, I. ORCID: https://orcid.org/0000-0002-2492-959X, Topalis, P. ORCID: https://orcid.org/0000-0002-1635-4810, Austin, C., Bouwman, B.A.M. ORCID: https://orcid.org/0000-0002-9827-9497, Crosetto, N., Altmüller, J. ORCID: https://orcid.org/0000-0003-4372-1521 and Garinis, G.A. ORCID: https://orcid.org/0000-0002-3200-5004
|
| 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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