title: UV-C irradiation delays mitotic progression by recruiting Mps1 to kinetochores.
abstract: The effect of UV irradiation on replicating cells during interphase has been studied extensively. However, how the mitotic cell responds to UV irradiation is less well defined. Herein, we found that UV-C irradiation (254 nm) increases recruitment of the spindle checkpoint proteins Mps1 and Mad2 to the kinetochore during metaphase, suggesting that the spindle assembly checkpoint (SAC) is reactivated. In accordance with this, cells exposed to UV-C showed delayed mitotic progression, characterized by a prolonged chromosomal alignment during metaphase. UV-C irradiation also induced the DNA damage response and caused a significant accumulation of γ-H2AX on mitotic chromosomes. Unexpectedly, the mitotic delay upon UV-C irradiation is not due to the DNA damage response but to the relocation of Mps1 to the kinetochore. Further, we found that UV-C irradiation activates Aurora B kinase. Importantly, the kinase activity of Aurora B is indispensable for full recruitment of Mps1 to the kinetochore during both prometaphase and metaphase. Taking these findings together, we propose that UV irradiation delays mitotic progression by evoking the Aurora B-Mps1 signaling cascade, which exerts its role through promoting the association of Mps1 with the kinetochore in metaphase.
authors.affiliation: Center for Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Youguo
authors.initials: Y
authors.lastname: Ling
authors.forename: Wenjun
authors.initials: W
authors.lastname: Wang
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Ma
authors.forename: Pingping
authors.initials: P
authors.lastname: Tan
authors.forename: Ting
authors.initials: T
authors.lastname: Song
authors.forename: Congwen
authors.initials: C
authors.lastname: Wei
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Xuedong
authors.initials: X
authors.lastname: Liu
authors.forename: Runlin Z
authors.initials: RZ
authors.lastname: Ma
authors.forename: Hui
authors.initials: H
authors.lastname: Zhong
authors.forename: Cheng
authors.initials: C
authors.lastname: Cao
authors.forename: Quanbin
authors.initials: Q
authors.lastname: Xu
mesh_terms: D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008677:Metaphase / Q000502:physiology* / Q000528:radiation effects; D008938:Mitosis / Q000528:radiation effects*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology* / Q000528:radiation effects; D059008:Time-Lapse Imaging; D014466:Ultraviolet Rays
chemical_list: D018797:Cell Cycle Proteins; D034741:RNA, Small Interfering; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C075840:TTK protein, human
keywords: Aurora B; Mps1 kinase; UV-C irradiation; kinetochore association; mitotic delay