Abstract B10: The role of Down syndrome's DYRK1A kinase in repair of the DNA double strand breaks

The function of DYRK1A protein kinase is regulated by its gene dosage whereby both gains and losses of one copy of DYRK1A gene on chromosome 21 result in developmental abnormalities. In order to better understand the function and regulation of DYRK1A, we applied a highly sensitive MudPIT proteomic approach to identify DYRK1A-interacting proteins in human cells. Four biological replicate MudPIT experiments were performed and the proteins reproducibly detected in the DYRK1A immunoprecipitates but not in the controls, were identified. Six proteins detected in all four biological replicate experiments were also most highly enriched in the DYRK1A immunoprecipitates, suggesting that these proteins form stable and abundant complexes with DYRK1A. One of these proteins, RNF169, has been recently characterized as a component of ubiquitin-mediated cascade involved in the repair of DNA double-strand breaks (DSBs). DSBs are deleterious DNA lesions that are repaired by hierarchical and orchestrated recruitment of multiple different proteins to a modified chromatin in the vicinity of the DNA damage sites. Presence of specific chromatin marks including ubiquitination regulates the choice between two major DSB repair pathways: homologous recombination repair (HRR) and non-homologous end joining (NHEJ), mediated by recruitment of chromatin-binding DNA damage response proteins including 53BP1 and RNF169. Binding of 53BP1 could prevent the resection of the DNA strands near the damage site necess...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: DNA Damage Signaling: Poster Presentations - Proffered Abstracts Source Type: research