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The Golgi complex is a regulatory hub for homologous recombination-mediated DNA repair.
The Golgi complex is a regulatory hub for homologous recombination-mediated DNA repair.
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Length:
20 minutes
Released:
Oct 17, 2022
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2022.10.17.512236v1?rss=1
Authors: Galea, G., Kuodyte, K., Khan, M. M., Thul, P. J., Neumann, B., Lundberg, E., Pepperkok, R.
Abstract:
Cells are constantly exposed to a multitude of DNA-damaging agents that can lead to mutation, dysregulation, and possibly cell death. To ensure genomic integrity, DNA Damage Response (DDR) mechanisms are set in motion to repair and mitigate any damage to the DNA structure. Although these pathways are well-studied in the context of nuclear function, relatively little is known of the regulatory function of cytoplasmic organelles. Here we show the first example of DDR regulation at the Golgi complex, coordinating Homologous Recombination (HR)-mediated DNA repair. We found that RAD51C, a regulatory HR protein, localises to the Golgi and nuclear compartments and in response to double-strand DNA breaks, the Golgi protein population of RAD51C redistributes to form nuclear foci. Furthermore, we found that the Golgi localisation of RAD51C is dependent on the Golgin Giantin. Depletion of Giantin induces the redistribution of the RAD51C Golgi pool to form nuclear foci, independent of DNA damage induction, and concurrent with a significant increase in genomic instability and inhibition of HR signalling regulators. This study presents evidence for a novel pathway where the Golgi is a central regulatory hub for HR DDR and potentially other repair pathways, a finding with important therapeutic implications.
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http://biorxiv.org/cgi/content/short/2022.10.17.512236v1?rss=1
Authors: Galea, G., Kuodyte, K., Khan, M. M., Thul, P. J., Neumann, B., Lundberg, E., Pepperkok, R.
Abstract:
Cells are constantly exposed to a multitude of DNA-damaging agents that can lead to mutation, dysregulation, and possibly cell death. To ensure genomic integrity, DNA Damage Response (DDR) mechanisms are set in motion to repair and mitigate any damage to the DNA structure. Although these pathways are well-studied in the context of nuclear function, relatively little is known of the regulatory function of cytoplasmic organelles. Here we show the first example of DDR regulation at the Golgi complex, coordinating Homologous Recombination (HR)-mediated DNA repair. We found that RAD51C, a regulatory HR protein, localises to the Golgi and nuclear compartments and in response to double-strand DNA breaks, the Golgi protein population of RAD51C redistributes to form nuclear foci. Furthermore, we found that the Golgi localisation of RAD51C is dependent on the Golgin Giantin. Depletion of Giantin induces the redistribution of the RAD51C Golgi pool to form nuclear foci, independent of DNA damage induction, and concurrent with a significant increase in genomic instability and inhibition of HR signalling regulators. This study presents evidence for a novel pathway where the Golgi is a central regulatory hub for HR DDR and potentially other repair pathways, a finding with important therapeutic implications.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Oct 17, 2022
Format:
Podcast episode
Titles in the series (100)
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