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Sökning: WFRF:(Reyes AL)

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  • Bravo, L, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Tabiri, S, et al. (författare)
  • 2021
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  • 2021
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  • Kanai, M, et al. (författare)
  • 2023
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  • 2017
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  • Niemi, MEK, et al. (författare)
  • 2021
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  • 2021
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  • Al-Behadili, Ali, et al. (författare)
  • A two-nuclease pathway involving RNase H1 is required for primer removal at human mitochondrial OriL
  • 2018
  • Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 46:18, s. 9471-9483
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of Ribonuclease H1 (RNase H1) during primer removal and ligation at the mitochondrial origin of light-strand DNA synthesis (OriL) is a key, yet poorly understood, step in mitochondrial DNA maintenance. Here, we reconstitute the replication cycle of L-strand synthesis in vitro using recombinant mitochondrial proteins and model OriL substrates. The process begins with initiation of DNA replication at OriL and ends with primer removal and ligation. We find that RNase H1 partially removes the primer, leaving behind the last one to three ribonucleotides. These 5'-end ribonucleotides disturb ligation, a conclusion which is supported by analysis of RNase H1-deficient patient cells. A second nuclease is therefore required to remove the last ribonucleotides and we demonstrate that Flap endonuclease 1 (FEN1) can execute this function in vitro. Removal of RNA primers at OriL thus depends on a two-nuclease model, which in addition to RNase H1 requires FEN1 or a FEN1-like activity. These findings define the role of RNase H1 at OriL and help to explain the pathogenic consequences of disease causing mutations in RNase H1.
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  • Bellenguez, C, et al. (författare)
  • New insights into the genetic etiology of Alzheimer's disease and related dementias
  • 2022
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
  • Tidskriftsartikel (refereegranskat)abstract
    • Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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  • Bouyoucef, S E, et al. (författare)
  • Poster Session 2 : Monday 4 May 2015, 08
  • 2015
  • Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
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  • Resultat 1-50 av 59

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