Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12530/27043
Title: DNA polymerase-α regulates the activation of type I interferons through cytosolic RNA:DNA synthesis.
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Issue Date: May-2016
Citation: Nat. Immunol..2016 May;(17)5:495-504
Abstract: Aberrant nucleic acids generated during viral replication are the main trigger for antiviral immunity, and mutations that disrupt nucleic acid metabolism can lead to autoinflammatory disorders. Here we investigated the etiology of X-linked reticulate pigmentary disorder (XLPDR), a primary immunodeficiency with autoinflammatory features. We discovered that XLPDR is caused by an intronic mutation that disrupts the expression of POLA1, which encodes the catalytic subunit of DNA polymerase-α. Unexpectedly, POLA1 deficiency resulted in increased production of type I interferons. This enzyme is necessary for the synthesis of RNA:DNA primers during DNA replication and, strikingly, we found that POLA1 is also required for the synthesis of cytosolic RNA:DNA, which directly modulates interferon activation. Together this work identifies POLA1 as a critical regulator of the type I interferon response.
PMID: 27019227
URI: https://hdl.handle.net/20.500.12530/27043
Rights: openAccess
Appears in Collections:Fundaciones e Institutos de Investigación > IIS H. U. Ramón y Cajal > Artículos

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