Abstract
Centrosome is an organelle that functions as a microtubule organizing center (MTOC) and regulates proper cell division. The centrosome consists of a pair of centrioles and the surrounding pericentriolar matrix (PCM). Overduplicated centrosomes cause multipolar spindle formation and unproper chromosome segregation. γ-tubulin, which is a component of PCM, provides microtubule anchoring machinery by forming a γ-tubulin ring complex (γ-TuRC). In our previous report, DNA damage proteins BRCA1 and NBS1 are involved in ubiquitination of γ-tubulin to regulate centrosome duplication.
Meanwhile, Fanconi Anemia (FA) is a rare genomic instability disorder characterized by chromosomal instability, bone marrow failure, and cancer predisposition. FA pathway is regulated by 13 FA proteins. FA core complex that consist of 8 of those FA proteins monoubiquitinate FANCD2 and FANCI as a E3 ubiquitinligase. This monoubiquitination is intensified by DNA damage. Monoubiquitinated FANCD2 and FANCI localize to DNA damage site and promote DNA repair. Recently, it was reported that FANCD2 localizes to discrete sites of mitotic chromosomes.
In this study, we investigated that whether FANCD2 is involved in centrosome maintenance in FA patients cells and FANCD2 knockdown cells.