Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Human RTEL1 associates with Poldip3 to facilitate responses to replication stress and R-loop resolution

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Parental Acceptance Rate of Testicular Tissue Cryopreservation in Danish Boys with Cryptorchidism

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Sertoli Cell Number Correlates with Serum Inhibin B in Infant Cryptorchid Boys

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Surgical Management of Undescended Testis - Timetable and Outcome: A Debate

    Research output: Contribution to journalReviewResearchpeer-review

  4. Mte1 interacts with Mph1 and promotes crossover recombination and telomere maintenance

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Burr hole craniostomy versus minicraniotomy in chronic subdural hematoma: a comparative cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. In response to: "Effective prophylaxis regimens against Cutibacterium acnes in Neurosurgery" by d'Alessandris et al

    Research output: Contribution to journalLetterResearchpeer-review

  3. Long-Term Follow-Up and Predictors of Functional Outcome after Surgery for Spinal Meningiomas: A Population-Based Cohort Study

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Risk factors for need of reoperation in bilateral chronic subdural haematomas

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Andrea Björkman
  • Søren L Johansen
  • Lin Lin
  • Mike Schertzer
  • Dimitris C Kanellis
  • Anna-Maria Katsori
  • Søren T Christensen
  • Yonglun Luo
  • Jens S Andersen
  • Simon J Elsässer
  • Arturo Londono-Vallejo
  • Jiri Bartek
  • Kenneth B Schou
View graph of relations

RTEL1 helicase is a component of DNA repair and telomere maintenance machineries. While RTEL1's role in DNA replication is emerging, how RTEL1 preserves genomic stability during replication remains elusive. Here we used a range of proteomic, biochemical, cell, and molecular biology and gene editing approaches to provide further insights into potential role(s) of RTEL1 in DNA replication and genome integrity maintenance. Our results from complementary human cell culture models established that RTEL1 and the Polδ subunit Poldip3 form a complex and are/function mutually dependent in chromatin binding after replication stress. Loss of RTEL1 and Poldip3 leads to marked R-loop accumulation that is confined to sites of active replication, enhances endogenous replication stress, and fuels ensuing genomic instability. The impact of depleting RTEL1 and Poldip3 is epistatic, consistent with our proposed concept of these two proteins operating in a shared pathway involved in DNA replication control under stress conditions. Overall, our data highlight a previously unsuspected role of RTEL1 and Poldip3 in R-loop suppression at genomic regions where transcription and replication intersect, with implications for human diseases including cancer.

Original languageEnglish
JournalGenes & Development
Volume34
Issue number15-16
Pages (from-to)1065-1074
Number of pages10
ISSN0890-9369
DOIs
Publication statusPublished - 1 Aug 2020

    Research areas

  • DNA damage response, DNA repair, DNA:RNA hybrid, Dyskeratosis congenita, Helicase, Hoyeral-hreiderson syndrome, Poldip3, Polymerase δ, POLδ, R-loop, RTEL1, Telomere maintenance

ID: 61380498