NUSAP1 influences the DNA damage response by controlling BRCA1 protein levels

摘要

NUSA P1 has been reported to function in mitotic spindle assembly, chromosome segregation, and regulation of cytokinesis. In this study, we find that NUSA P1 has hitherto unknown functions in the key BRCA 1-regulated pathways of double strand DNA break repair and centrosome duplication. Both these pathways are important for maintenance of genomic stability, and any defects in these pathways can cause tumorigenesis. Depletion of NUSA P1 from cells led to the suppression of double strand DNA break repair via the homologous recombination and single-strand annealing pathways. The presence of NUSA P1 was also found to be important for the control of centrosome numbers. We have found evidence that NUSA P1 plays a role in these processes through regulation of BRCA 1 protein levels, and BRCA 1 overexpression from a plasmid mitigates the defective phenotypes seen upon NUSA P1 depletion. We found that after NUSA P1 depletion there is a decrease in BRCA 1 recruitment to ionizing radiation-induced foci. Results from this study reveal a novel association between BRCA 1 and NUSA P1 and suggests a mechanism whereby NUSA P1 is involved in carcinogenesis.