title: NUSAP1 influences the DNA damage response by controlling BRCA1 protein levels.
abstract: NUSAP1 has been reported to function in mitotic spindle assembly, chromosome segregation, and regulation of cytokinesis. In this study, we find that NUSAP1 has hitherto unknown functions in the key BRCA1-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 NUSAP1 from cells led to the suppression of double strand DNA break repair via the homologous recombination and single-strand annealing pathways. The presence of NUSAP1 was also found to be important for the control of centrosome numbers. We have found evidence that NUSAP1 plays a role in these processes through regulation of BRCA1 protein levels, and BRCA1 overexpression from a plasmid mitigates the defective phenotypes seen upon NUSAP1 depletion. We found that after NUSAP1 depletion there is a decrease in BRCA1 recruitment to ionizing radiation-induced foci. Results from this study reveal a novel association between BRCA1 and NUSAP1 and suggests a mechanism whereby NUSAP1 is involved in carcinogenesis.
authors: Department of Biomedical Informatics; The Ohio State University Comprehensive Cancer Center; The Ohio State University; Columbus, OH USA.
authors: Shweta
authors: S
authors: Kotian
authors: Department of Biomedical Informatics; The Ohio State University Comprehensive Cancer Center; The Ohio State University; Columbus, OH USA.
authors: Tapahsama
authors: T
authors: Banerjee
authors: Department of Biomedical Informatics; The Ohio State University Comprehensive Cancer Center; The Ohio State University; Columbus, OH USA.
authors: Ainsley
authors: A
authors: Lockhart
authors: Department of Biomedical Informatics; The Ohio State University Comprehensive Cancer Center; The Ohio State University; Columbus, OH USA.
authors: Kun
authors: K
authors: Huang
authors: Department of Biomedical Informatics; The Ohio State University Comprehensive Cancer Center; The Ohio State University; Columbus, OH USA.
authors: Umit V
authors: UV
authors: Catalyurek
authors: Department of Biomedical Informatics; The Ohio State University Comprehensive Cancer Center; The Ohio State University; Columbus, OH USA.
authors: Jeffrey D
authors: JD
authors: Parvin
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D018385:Centrosome / Q000378:metabolism; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints; D059765:Homologous Recombination; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D059807:S Phase Cell Cycle Checkpoints
chemical_list: D019313:BRCA1 Protein; D004277:DNA, Single-Stranded; D008869:Microtubule-Associated Proteins; C000709213:NUSAP1 protein, human
keywords: BRCA1; DNA repair; NUSAP1; centrosomes; homologous recombination