The microprocessing factor DGCR8 interacts with ATM and functions independently of its partner DROSHA in the DDR

The eukaryotic cell has evolved a complex suite of mechanisms called the DNA damage response (DDR), that acts by sensing DNA damage and reacting appropriately to maintain genomic integrity. The PIK kinase ATM is a key orchestrator of the DDR. In this study we map the interaction between the miRNA processing factor DGCR8 and ATM. We investigate the role of DGCR8 in the DDR and also assess the involvement of its miRNA processing partner DROSHA in the DDR. We propose that DGCR8 is functioning as a negative regulator of ATM and is functioning separately of DROSHA in the DDR. Another ATM interacting factor, RSF1 was previously shown to be required for the recruitment of the CENP-S/-X complex to DSBs. In this study we also generate a novel antibody reagent raised against the CENP-S/-X complex with the aim of mapping the distribution of the CENP-S/-X complex at DSBs by ChIP-Seq. We attempt to map the distribution of CENP-S/-X and CENP-A at satellite free centromeres to determine if our novel antibody is of ChIP-grade.

Publisher

NUI Galway

Rights

Attribution-NonCommercial-NoDerivs 3.0 Ireland

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Collections

University of Galway Theses (PhD Theses)