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A DNA damage response (DDR), particularly on double-stranded breaks (DSBs); RNF8 and RNF168 are crucial E3 ligases that are recruited first to the site of DNA damage. RNF8 initiates the conjugation of ubiquitin with H2A and H2AX, subsequently, RNF168 is employed to amplify the K-63-linked ubiquitin chain. These two E3 ligases are necessary for the downstream signaling where 53BP1 and BRCA1 are recruited. RNF168 directs 53BP1 involvement in non-homologous end joining (NHEJ) but is unable to save BRCA1 which is involved in homologous recombination (HR); therefore, it is RNF8 that plays a huge role in the recruitment of BRCA1. As recently BRCA1 has come up as a potential E3 ligase in Alzheimer's disease (AD) and damage to its heterodimeric partner BARD1 results in mislocalization of BRCA1 to cytosol that further joins tau lesion. Therefore, in this cumbersome signaling cascade, we took …