53BP1 is known as a mediator in DNA damage response and a regulator of DNA double-stranded breaks (DSBs) repair. 53BP1 was recently reported to be a centrosomal protein and a binding partner of mitotic polo-like kinase 1 (Plk1). The stability of 53BP1, in response to DSBs, is regulated by its phosphorylation, deubiquitination, and ubiquitination. During mitosis, 53BP1 is stabilized by phosphorylation at S380, a putative binding region with polo-box domain of Plk1, and deubiquitination by ubiquitin-specific protease 7 (USP7). In the absence of DSBs, 53BP1 is abundant in the nucleoplasm; DSB formation results in its rapid localization to the damaged chromatin. Mitotic 53BP1 is also localized at the centrosome and spindle pole. 53BP1 depletion induces mitotic defects such as disorientation of spindle poles attributed to extra centrosomes or mispositioning of centrosomes, leading to phenotypes similar to those in USP7-deficient cells. Here, we discuss how 53BP1 controls the centrosomal integrity through its interaction with USP7 and centromere protein F by regulation of its stability and its physiology in response to DNA damage.