Active DNA damage eviction by HLTF stimulates nucleotide excision repair
| Autor: | Marvin van Toorn, Yasemin Turkyilmaz, Sueji Han, Di Zhou, Hyun-Suk Kim, Irene Salas-Armenteros, Mihyun Kim, Masaki Akita, Franziska Wienholz, Anja Raams, Eunjin Ryu, Sukhyun Kang, Arjan F. Theil, Karel Bezstarosti, Maria Tresini, Giuseppina Giglia-Mari, Jeroen A. Demmers, Orlando D. Schärer, Jun-Hyuk Choi, Wim Vermeulen, Jurgen A. Marteijn |
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| Přispěvatelé: | Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Science and Technology [Daejeon] (UST), Institute for Basic Science (IBS), Pusan National University, Ulsan National Institute of Science and Technology (UNIST), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Giglia-Mari, Ambra, Molecular Genetics, Biochemistry |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
DNA Replication
post-replication repair DNA Repair TFIIH [SDV]Life Sciences [q-bio] damage eviction DNA Cell Biology repair synthesis HLTF nucleotide excision repair Article UV damage response DNA-Binding Proteins [SDV] Life Sciences [q-bio] SDG 3 - Good Health and Well-being DNA damage Molecular Biology genome stability |
| Zdroj: | Molecular Cell Molecular Cell, 2022, 82 (7), pp.1343-1358.e8. ⟨10.1016/j.molcel.2022.02.020⟩ Molecular Cell, 82(7), 1343-1358.e8. Cell Press Mol Cell |
| ISSN: | 1097-4164 1097-2765 |
| Popis: | International audience; Nucleotide excision repair (NER) counteracts the onset of cancer and aging by removing helix-distorting DNA lesions via a "cut-and-patch"-type reaction. The regulatory mechanisms that drive NER through its successive damage recognition, verification, incision, and gap restoration reaction steps remain elusive. Here, we show that the RAD5-related translocase HLTF facilitates repair through active eviction of incised damaged DNA together with associated repair proteins. Our data show a dual-incision-dependent recruitment of HLTF to the NER incision complex, which is mediated by HLTF's HIRAN domain that binds 3'-OH single-stranded DNA ends. HLTF's translocase motor subsequently promotes the dissociation of the stably damage-bound incision complex together with the incised oligonucleotide, allowing for an efficient PCNA loading and initiation of repair synthesis. Our findings uncover HLTF as an important NER factor that actively evicts DNA damage, thereby providing additional quality control by coordinating the transition between the excision and DNA synthesis steps to safeguard genome integrity. |
| Databáze: | OpenAIRE |
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