SLX4 interacts with RTEL1 to prevent transcription-mediated DNA replication perturbations.

Autor: Takedachi A; Centre de Recherche en Cancérologie de Marseille, CRCM, Inserm, CNRS, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, France.; Inovarion, Paris, France.; Department of Chemistry, Faculty of Science, Fukuoka University, Fukuoka, Japan., Despras E; CNRS UMR9019, Université Paris-Saclay, Equipe labellisée Ligue contre le Cancer, Gustave Roussy, Villejuif, France., Scaglione S; Centre de Recherche en Cancérologie de Marseille, CRCM, Inserm, CNRS, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, France., Guérois R; Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette cedex, France., Guervilly JH; Centre de Recherche en Cancérologie de Marseille, CRCM, Inserm, CNRS, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, France., Blin M; Centre de Recherche en Cancérologie de Marseille, CRCM, Inserm, CNRS, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, France., Audebert S; Centre de Recherche en Cancérologie de Marseille, CRCM, Inserm, CNRS, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, France., Camoin L; Centre de Recherche en Cancérologie de Marseille, CRCM, Inserm, CNRS, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, France., Hasanova Z; Centre de Recherche en Cancérologie de Marseille, CRCM, Inserm, CNRS, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, France.; Institute of Molecular Genetics, Prague, Czech Republic., Schertzer M; Institut Curie, PSL Research University, CNRS, UMR3244, Paris, France.; Sorbonne Universités, UPMC Univ. Paris 06, CNRS, UMR3244, Paris, France., Guille A; Centre de Recherche en Cancérologie de Marseille, CRCM, Inserm, CNRS, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, France., Churikov D; Centre de Recherche en Cancérologie de Marseille, CRCM, Inserm, CNRS, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, France., Callebaut I; Sorbonne Université, Muséum National d'Histoire Naturelle, UMR CNRS 7590, IRD, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Paris, France., Naim V; CNRS UMR9019, Université Paris-Saclay, Gustave Roussy, Villejuif, France., Chaffanet M; Centre de Recherche en Cancérologie de Marseille, CRCM, Inserm, CNRS, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, France., Borg JP; Centre de Recherche en Cancérologie de Marseille, CRCM, Inserm, CNRS, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, France., Bertucci F; Centre de Recherche en Cancérologie de Marseille, CRCM, Inserm, CNRS, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, France., Revy P; INSERM UMR 1163, Laboratory of Genome Dynamics in the Immune System, Equipe Labellisée La Ligue contre le Cancer, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France., Birnbaum D; Centre de Recherche en Cancérologie de Marseille, CRCM, Inserm, CNRS, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, France., Londoño-Vallejo A; Institut Curie, PSL Research University, CNRS, UMR3244, Paris, France.; Sorbonne Universités, UPMC Univ. Paris 06, CNRS, UMR3244, Paris, France., Kannouche PL; CNRS UMR9019, Université Paris-Saclay, Equipe labellisée Ligue contre le Cancer, Gustave Roussy, Villejuif, France., Gaillard PHL; Centre de Recherche en Cancérologie de Marseille, CRCM, Inserm, CNRS, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, France. pierre-henri.gaillard@inserm.fr.
Jazyk: angličtina
Zdroj: Nature structural & molecular biology [Nat Struct Mol Biol] 2020 May; Vol. 27 (5), pp. 438-449. Date of Electronic Publication: 2020 May 11.
DOI: 10.1038/s41594-020-0419-3
Abstrakt: The SLX4 tumor suppressor is a scaffold that plays a pivotal role in several aspects of genome protection, including homologous recombination, interstrand DNA crosslink repair and the maintenance of common fragile sites and telomeres. Here, we unravel an unexpected direct interaction between SLX4 and the DNA helicase RTEL1, which, until now, were viewed as having independent and antagonistic functions. We identify cancer and Hoyeraal-Hreidarsson syndrome-associated mutations in SLX4 and RTEL1, respectively, that abolish SLX4-RTEL1 complex formation. We show that both proteins are recruited to nascent DNA, tightly co-localize with active RNA pol II, and that SLX4, in complex with RTEL1, promotes FANCD2/RNA pol II co-localization. Importantly, disrupting the SLX4-RTEL1 interaction leads to DNA replication defects in unstressed cells, which are rescued by inhibiting transcription. Our data demonstrate that SLX4 and RTEL1 interact to prevent replication-transcription conflicts and provide evidence that this is independent of the nuclease scaffold function of SLX4.
Databáze: MEDLINE
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