FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3085202612> ?p ?o ?g. }

• W3085202612 abstract "Abstract Mutations in POLG , encoding POLγA, the catalytic subunit of the mitochondrial DNA polymerase, cause a spectrum of disorders characterized by mtDNA instability. However, the molecular pathogenesis of POLG -related diseases is poorly understood and efficient treatments are missing. Here, we generated a POLG A449T/A449T mouse model, which reproduces the most common human recessive mutation of POLG , encoding the A467T change, and dissected the mechanisms underlying pathogenicity. We show that the A449T mutation impairs DNA binding and mtDNA synthesis activities of POLγ in vivo and in vitro . Interestingly, the A467T mutation also strongly impairs interactions with POLγB, the homodimeric accessory subunit of holo-POLγ. This allows the free POLγA to become a substrate for LONP1 protease degradation, leading to dramatically reduced levels of POLγA, which in turn exacerbates the molecular phenotypes of Polg A449T/A449T mice. Importantly, we validated this mechanism for other mutations affecting the interaction between the two POLγ subunits. We suggest that LONP1 dependent degradation of POLγA can be exploited as a target for the development of future therapies." @default.
• W3085202612 created "2020-09-21" @default.
• W3085202612 creator A5001301469 @default.
• W3085202612 creator A5005070331 @default.
• W3085202612 creator A5006795555 @default.
• W3085202612 creator A5035679168 @default.
• W3085202612 creator A5036499932 @default.
• W3085202612 creator A5043211179 @default.
• W3085202612 creator A5048857899 @default.
• W3085202612 creator A5054899752 @default.
• W3085202612 creator A5059013142 @default.
• W3085202612 creator A5060623628 @default.
• W3085202612 creator A5061459911 @default.
• W3085202612 creator A5061928867 @default.
• W3085202612 creator A5068121199 @default.
• W3085202612 creator A5078967142 @default.
• W3085202612 creator A5083800659 @default.
• W3085202612 creator A5083821696 @default.
• W3085202612 creator A5084403450 @default.
• W3085202612 creator A5087608233 @default.
• W3085202612 creator A5090033227 @default.
• W3085202612 creator A5090817128 @default.
• W3085202612 date "2020-09-12" @default.
• W3085202612 modified "2023-10-16" @default.
• W3085202612 title "In vivo and in vitro mechanistic characterization of a clinically relevant PolγA mutation" @default.
• W3085202612 cites W1495866683 @default.
• W3085202612 cites W1551996591 @default.
• W3085202612 cites W1853661044 @default.
• W3085202612 cites W1968197570 @default.
• W3085202612 cites W1979809549 @default.
• W3085202612 cites W1983386499 @default.
• W3085202612 cites W2001256046 @default.
• W3085202612 cites W2001294987 @default.
• W3085202612 cites W2006249760 @default.
• W3085202612 cites W2010300247 @default.
• W3085202612 cites W2026779731 @default.
• W3085202612 cites W2030230379 @default.
• W3085202612 cites W2030608692 @default.
• W3085202612 cites W2031782684 @default.
• W3085202612 cites W2032606344 @default.
• W3085202612 cites W2076224048 @default.
• W3085202612 cites W2077446001 @default.
• W3085202612 cites W2077517552 @default.
• W3085202612 cites W2089135250 @default.
• W3085202612 cites W2089172085 @default.
• W3085202612 cites W2104250033 @default.
• W3085202612 cites W2105911051 @default.
• W3085202612 cites W2117795149 @default.
• W3085202612 cites W2118918028 @default.
• W3085202612 cites W2121594663 @default.
• W3085202612 cites W2131507123 @default.
• W3085202612 cites W2135606644 @default.
• W3085202612 cites W2145275398 @default.
• W3085202612 cites W2146482482 @default.
• W3085202612 cites W2147828523 @default.
• W3085202612 cites W2152058227 @default.
• W3085202612 cites W2156503106 @default.
• W3085202612 cites W2167764669 @default.
• W3085202612 cites W2215582843 @default.
• W3085202612 cites W2226363993 @default.
• W3085202612 cites W2444473506 @default.
• W3085202612 cites W2520257246 @default.
• W3085202612 cites W2585982412 @default.
• W3085202612 cites W2900457101 @default.
• W3085202612 cites W3011930227 @default.
• W3085202612 cites W3030119061 @default.
• W3085202612 doi "https://doi.org/10.1101/2020.09.10.291369" @default.
• W3085202612 hasPublicationYear "2020" @default.
• W3085202612 type Work @default.
• W3085202612 sameAs 3085202612 @default.
• W3085202612 citedByCount "0" @default.
• W3085202612 crossrefType "posted-content" @default.
• W3085202612 hasAuthorship W3085202612A5001301469 @default.
• W3085202612 hasAuthorship W3085202612A5005070331 @default.
• W3085202612 hasAuthorship W3085202612A5006795555 @default.
• W3085202612 hasAuthorship W3085202612A5035679168 @default.
• W3085202612 hasAuthorship W3085202612A5036499932 @default.
• W3085202612 hasAuthorship W3085202612A5043211179 @default.
• W3085202612 hasAuthorship W3085202612A5048857899 @default.
• W3085202612 hasAuthorship W3085202612A5054899752 @default.
• W3085202612 hasAuthorship W3085202612A5059013142 @default.
• W3085202612 hasAuthorship W3085202612A5060623628 @default.
• W3085202612 hasAuthorship W3085202612A5061459911 @default.
• W3085202612 hasAuthorship W3085202612A5061928867 @default.
• W3085202612 hasAuthorship W3085202612A5068121199 @default.
• W3085202612 hasAuthorship W3085202612A5078967142 @default.
• W3085202612 hasAuthorship W3085202612A5083800659 @default.
• W3085202612 hasAuthorship W3085202612A5083821696 @default.
• W3085202612 hasAuthorship W3085202612A5084403450 @default.
• W3085202612 hasAuthorship W3085202612A5087608233 @default.
• W3085202612 hasAuthorship W3085202612A5090033227 @default.
• W3085202612 hasAuthorship W3085202612A5090817128 @default.
• W3085202612 hasBestOaLocation W30852026121 @default.
• W3085202612 hasConcept C104292427 @default.
• W3085202612 hasConcept C104317684 @default.
• W3085202612 hasConcept C143425029 @default.
• W3085202612 hasConcept C153911025 @default.
• W3085202612 hasConcept C24586158 @default.
• W3085202612 hasConcept C2756471 @default.
• W3085202612 hasConcept C501734568 @default.

• next