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Centrosome dysfunction associated with somatic expression of the synaptonemal complex protein TEX12

Lookup NU author(s): Dr Jill Hunter, Lucy Salmon, Dr Caroline WilsonORCiD, Professor Neil PerkinsORCiD, Dr Owen Davies

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 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.


Publication metadata

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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Funding

Funder referenceFunder name
ORD previously a Sir Henry Dale Fellow jointly funded by the Wellcome Trust and Royal Society (Grant Number 104158/Z/14/Z).
O.R.D. is a Wellcome Trust Senior Research Fellow (Grant Number 219413/Z/19/Z)

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