Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/119791
Title: THE STRUCTURE-SPECIFIC ENDONUCLEASE MUS81 MEDIATES STING-DEPENDENT IMMUNE RECOGNITION OF PROSTRATE TUMOUR CELLS
Authors: HO SHU WEN SAMANTHA
Keywords: Cytosolic DNA, Cancer, Endonuclease, DNA repair
Issue Date: 9-Jan-2015
Citation: HO SHU WEN SAMANTHA (2015-01-09). THE STRUCTURE-SPECIFIC ENDONUCLEASE MUS81 MEDIATES STING-DEPENDENT IMMUNE RECOGNITION OF PROSTRATE TUMOUR CELLS. ScholarBank@NUS Repository.
Abstract: THE PROCESSING OF STALLED REPLICATION FORKS IS CRITICAL FOR THE MAINTENANCE OF GENOME STABILITY AND SURVIVAL OF ORGANISMS. THE DNA STRUCTURE-SPECIFIC ENDONUCLEASE MUS81 PLAYS AN IMPORTANT ROLE IN THE REPAIR OF STALLED REPLICATION FORKS. HERE, WE SHOW THAT CLEAVAGE OF GENOMIC DNA BY MUS81 LEADS TO THE PRESENCE OF DNA IN THE CYTOSOL IN TUMOR CELLS. OVEREXPRESSION OF MUS81 INDUCED THE PRESENCE OF CYTOSOLIC DNA IN MUS81-/- MOUSE EMBRYONIC FIBROBLASTS (MEFS) AND THE ARTIFICIAL MUS81 SUBSTRATE PAT25TETA IN THE CYTOSOL OF PAT25TETA+ MUS81-/- MEFS. IMPAIRED EXPRESSION OF MUS81 DECREASED THE CONSTITUTIVE LEVELS OF CYTOSOLIC DNA PRESENT IN PROSTATE TUMOR CELLS. MUS81-INDUCED CYTOSOLIC DNA ACTIVATES STING-DEPENDENT INNATE IMMUNE PATHWAYS LEADING TO EXPRESSION OF TYPE I INTERFERONS (IFN). THE TYPE I IFN-MEDIATED IMMUNE REJECTION OF TUMOR CELLS DEPENDED ON IFN-? AND INCREASED PHAGOCYTOSIS OF TUMOR CELLS BY MACROPHAGES AS A RESULT OF DEREGULATED PRO-PHAGOCYTIC SIGNALS. IN SUMMARY, REPAIR OF GENOM
URI: http://scholarbank.nus.edu.sg/handle/10635/119791
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