KIF18B, a nuclear kinesin, is involved in DNA damage response
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DNA damage from both exogenous and endogenous sources occurs continuously in all cells. A multitude of DNA repair mechanisms have evolved to maintain genome stability. The 53BP1 tumour suppressor has been identified as a so-called mediator of the DNA double-strand break repair, promoting simple joining of breaks rather than a complex process of using an intact homologous strand as a template for repair. Additionally, 53BP1 is critical for class switch recombination in B-cells, a fusion of de-protected telomeres, and promotes the mobility of the broken ends of chromosomes. A previous proteomic screen for interacting partners of 53BP1 identified a kinesin, KIF18B, as a novel interactor. This interaction occurs via the Tudor domain of 53BP1 and a newly identified Tudor Interacting Motif (TIM) in KIF18B. KIF18B is a kinesin-8 family member with a known role in maintaining the length of astral microtubules. Here we investigated the involvement of KIF18B in the DNA damage response and found it to be mainly nuclear in interphase and localised to DNA damage sites. We have also shown that 53BP1 focal recruitment to sites of DNA damage is KIF18B dependent. Furthermore, KIF18B is involved in the fusion of deprotected telomeres. Telomere fusion and 53BP1 recruitment to Telomere Dysfunction-Induced Foci requires TIM, as well as the motor domain of KIF18B. Based on our observations, we propose a role for KIF18B in DNA damage response through mediating 53BP1 dependent DNA double-strand break mobility. Besides, we established that the KIF18B protein expression is cell cycle-regulated, which increases as cells move from G1 to mitosis, and returns to low levels in late mitosis and early G1. Interestingly, we also showed specific localisation of KIF18B to the midbody of cytokinetic cells, suggesting a role for KIF18B in abscission.
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