解旋酶
RNA解旋酶A
永恒的
抄写(语言学)
DNA修复
遗传学
生物
DNA复制
细胞生物学
DNA
核糖核酸
基因
语言学
昼夜节律
哲学
神经科学
作者
Arato Takedachi,Emmanuelle Despras,Sarah Scaglione,Raphaël Guérois,Jean-Hugues Guervilly,Marion Blin,Stéphane Audebert,Luc Camoin,Zdenka Hašanová,Michael Schertzer,Arnaud Guillé,Dmitri Churikov,Isabelle Callebaut,Valeria Naim,Max Chaffanet,Jean‐Paul Borg,François Bertucci,Patrick Revy,Daniel Birnbaum,Arturo Londoño‐Vallejo
标识
DOI:10.1038/s41594-020-0419-3
摘要
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. Biochemical characterization of the complex formed by tumor suppressor SLX4 and RTEL1 helicase reveals a role in genome integrity maintenance as well as how their interaction is impaired by disease-associated mutations.
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