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Lookup NU author(s): Dr Jill Hunter, Lucy Salmon, Dr Caroline WilsonORCiD, Professor Neil PerkinsORCiD, Dr Owen Davies
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021, The Author(s).The synaptonemal complex (SC) is a supramolecular protein scaffold that mediates chromosome synapsis and facilitates crossing over during meiosis. In mammals, SC proteins are generally assumed to have no other function. Here, we show that SC protein TEX12 also localises to centrosomes during meiosis independently of chromosome synapsis. In somatic cells, ectopically expressed TEX12 similarly localises to centrosomes, where it is associated with centrosome amplification, a pathology correlated with cancer development. Indeed, TEX12 is identified as a cancer-testis antigen and proliferation of some cancer cells is TEX12-dependent. Moreover, somatic expression of TEX12 is aberrantly activated via retinoic acid signalling, which is commonly disregulated in cancer. Structure-function analysis reveals that phosphorylation of TEX12 on tyrosine 48 is important for centrosome amplification but not for recruitment of TEX12 to centrosomes. We conclude that TEX12 normally localises to meiotic centrosomes, but its misexpression in somatic cells can contribute to pathological amplification and dysfunction of centrosomes in cancers.
Author(s): Sandhu S, Sou IF, Hunter JE, Salmon L, Wilson CL, Perkins ND, Hunter N, Davies OR, McClurg UL
Publication type: Article
Publication status: Published
Journal: Communications Biology
Year: 2021
Volume: 4
Issue: 1
Online publication date: 08/12/2021
Acceptance date: 12/11/2021
Date deposited: 13/01/2022
ISSN (electronic): 2399-3642
Publisher: Nature Research
URL: https://doi.org/10.1038/s42003-021-02887-4
DOI: 10.1038/s42003-021-02887-4
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