scholarly journals Hydroxychloroquine modulates immunological pathways activated by RNA:DNA hybrids in Aicardi–Goutières syndrome patients carrying RNASEH2 mutations

Author(s):  
Jessica Garau ◽  
Daisy Sproviero ◽  
Francesca Dragoni ◽  
Elisa Piscianz ◽  
Carolina Santonicola ◽  
...  
Keyword(s):  
2020 ◽  
Vol 61 (6) ◽  
pp. 1107-1119
Author(s):  
Jan Kuciński ◽  
Sebastian Chamera ◽  
Aleksandra Kmera ◽  
M Jordan Rowley ◽  
Sho Fujii ◽  
...  

Abstract RNase H1 is an endonuclease specific toward the RNA strand of RNA:DNA hybrids. Members of this protein family are present in most living organisms and are essential for removing RNA that base pairs with DNA. It prevents detrimental effects of RNA:DNA hybrids and is involved in several biological processes. Arabidopsis thaliana has been previously shown to contain three genes encoding RNase H1 proteins that localize to three distinct cellular compartments. We show that these genes originate from two gene duplication events. One occurred in the common ancestor of dicots and produced nuclear and organellar RNase H1 paralogs. Second duplication occurred in the common ancestor of Brassicaceae and produced mitochondrial- and plastid-localized proteins. These proteins have the canonical RNase H1 activity, which requires at least four ribonucleotides for endonucleolytic digestion. Analysis of mutants in the RNase H1 genes revealed that the nuclear RNH1A and mitochondrial RNH1B are dispensable for development under normal growth conditions. However, the presence of at least one organellar RNase H1 (RNH1B or RNH1C) is required for embryonic development. The plastid-localized RNH1C affects plastid DNA copy number and sensitivity to replicative stress. Our results present the evolutionary history of RNH1 proteins in A. thaliana, demonstrate their canonical RNase H1 activity and indicate their role in early embryonic development.


2020 ◽  
Vol 784 ◽  
pp. 108300 ◽  
Author(s):  
Alessandra Brambati ◽  
Luca Zardoni ◽  
Eleonora Nardini ◽  
Achille Pellicioli ◽  
Giordano Liberi
Keyword(s):  

Cell ◽  
1977 ◽  
Vol 11 (4) ◽  
pp. 819-836 ◽  
Author(s):  
Louise T. Chow ◽  
James M. Roberts ◽  
James B. Lewis ◽  
Thomas R. Broker

Gene ◽  
1985 ◽  
Vol 39 (1) ◽  
pp. 77-83 ◽  
Author(s):  
Frederick S. Jones ◽  
Jacob I. Grimberg ◽  
Stuart G. Fischer ◽  
John P. Ford

2015 ◽  
Vol 112 (18) ◽  
pp. 5779-5784 ◽  
Author(s):  
Ruth Stuckey ◽  
Néstor García-Rodríguez ◽  
Andrés Aguilera ◽  
Ralf Erik Wellinger

DNA replication initiates at defined replication origins along eukaryotic chromosomes, ensuring complete genome duplication within a single S-phase. A key feature of replication origins is their ability to control the onset of DNA synthesis mediated by DNA polymerase-α and its intrinsic RNA primase activity. Here, we describe a novel origin-independent replication process that is mediated by transcription. RNA polymerase I transcription constraints lead to persistent RNA:DNA hybrids (R-loops) that prime replication in the ribosomal DNA locus. Our results suggest that eukaryotic genomes have developed tools to prevent R-loop–mediated replication events that potentially contribute to copy number variation, particularly relevant to carcinogenesis.


2020 ◽  
Author(s):  
S Cohen ◽  
A Guenolé ◽  
A Marnef ◽  
T Clouaire ◽  
N Puget ◽  
...  

AbstractTranscriptionally active loci are particularly prone to breakage and mounting evidence suggest that DNA Double-Strand Breaks arising in genes are handled by a dedicated repair pathway, Transcription-Coupled DSB Repair (TC-DSBR), that entails R-loops accumulation and dissolution. Here, we uncovered a critical function of the Bloom RecQ DNA helicase (BLM) in TC-DSBR in human cells. BLM is recruited in a transcription dependent-manner at DSBs where it fosters resection, RAD51 binding and accurate Homologous Recombination repair. However, in a R-loop dissolution-deficient background BLM switches from promoting Homologous Recombination to promoting Break-Induced Replication (BIR), which strongly impairs cell viability. Altogether our work unveils a role for BLM in BIR at DSBs in active chromatin, and highlights the toxic potential of RNA:DNA hybrids that accumulate at these transcription-associated DSBs.


Sign in / Sign up

Export Citation Format

Share Document