IMR Press / FBL / Volume 23 / Issue 1 / DOI: 10.2741/4577

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Review

53BP1: A guardian for centrosomal integrity

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1 Department of Biological and Health Sciences, Texas A & M University-Kingsville, Kingsville, TX 78363, USA
2 Department of Pharmacy, College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do 15588, Korea
Front. Biosci. (Landmark Ed) 2018, 23(1), 1–12;
Published: 1 January 2018
(This article belongs to the Special Issue DNA damage, DNA repair, and DNA damage response pathways)

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.

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