Characterisation of two deubiquitinating enzymes in the DNA damage response and replication
作者： Helen Rosemary Stone
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摘要: Ub has an essential role within the DNA double strand break (DSB) response which is well documented. However of ubiquitin (Ub) in regulation replication emerging area research. This thesis investigates how two deubiquitinating enzymes (DUBs) regulate DSB repair and respectively. A screen 103 siRNAs against putative DUBs human genome, measuring amount conjugated after release from HU-induced damage, identified proteasome associated DUB, POH1 as being important regulating Ub-conjuagtes damage. Further work found that restricts K63-linked at DSBs consequently 53BP1 foci formation. appears to breaks by Non-homologous end-joining (NHEJ). The DUB also another having significantly reduced levels shown have a preventing formation Mus81-dependent during replication, with depletion sensitising cells replication-stress. Therefore this works demonstrates for genomic stability replication. In I demonstrate these respectively, providing potential therapeutic targets.
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