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dc.contributor.authorHill, Sarah
dc.contributor.authorMordes, Daniel
dc.contributor.authorCameron, Lisa
dc.contributor.authorNeuberg, Donna
dc.contributor.authorLandini, Serena
dc.contributor.authorEggan, Kevin
dc.contributor.authorLivingston, David
dc.date.accessioned2019-10-03T14:38:20Z
dc.date.issued2016
dc.identifier.citationHill, Sarah J., Daniel A. Mordes, Lisa A. Cameron, Donna S. Neuberg, Serena Landini, Kevin Eggan, and David M. Livingston. 2016. “Two Familial ALS Proteins Function in Prevention/Repair of Transcription-Associated DNA Damage.” Proceedings of the National Academy of Sciences 113 (48): E7701–9. https://doi.org/10.1073/pnas.1611673113.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41461192*
dc.description.abstractAmyotrophic lateral sclerosis (ALS) is a progressive motor neuron dysfunction disease that leads to paralysis and death. There is currently no established molecular pathogenesis pathway. Multiple proteins involved in RNA processing are linked to ALS, including FUS and TDP43, and we propose a disease mechanism in which loss of function of at least one of these proteins leads to an accumulation of transcription-associated DNA damage contributing to motor neuron cell death and progressive neurological symptoms. In support of this hypothesis, we find that FUS or TDP43 depletion leads to increased sensitivity to a transcription-arresting agent due to increased DNA damage. Thus, these proteins normally contribute to the prevention or repair of transcription-associated DNA damage. In addition, both FUS and TDP43 colocalize with active RNA polymerase II at sites of DNA damage along with the DNA damage repair protein, BRCA1, and FUS and TDP43 participate in the prevention or repair of R loop-associated DNA damage, a manifestation of aberrant transcription and/or RNA processing. Gaining a better understanding of the role(s) that FUS and TDP43 play in transcription-associated DNA damage could shed light on the mechanisms underlying ALS pathogenesis.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleTwo familial ALS proteins function in prevention/repair of transcription-associated DNA damage
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dash.depositing.authorEggan, Kevin::0f3c57f5dab3376e0b3c0b177b709475::600
dc.date.available2019-10-03T14:38:20Z
dash.workflow.comments1Science Serial ID 91427
dc.identifier.doi10.1073/pnas.1611673113
dash.source.volume113;48
dash.source.pageE7701


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