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

DOI: 10.1038/s42003-021-02887-4 DOI Help

Authors: Sumit Sandhu (University of California, Davis) , Ieng F. Sou (University of Liverpool) , Jill E. Hunter (Newcastle University) , Lucy Salmon (Newcastle University) , Caroline L. Wilson (Newcastle University) , Neil D. Perkins (Newcastle University) , Neil Hunter (University of California, Davis) , Owen R. Davies (Newcastle University; University of Edinburgh) , Urszula L. Mcclurg (University of Liverpool)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Communications Biology , VOL 4

State: Published (Approved)
Published: December 2021
Diamond Proposal Number(s): 15836

Open Access Open Access

Abstract: 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.

Journal Keywords: Cell growth; Meiosis

Subject Areas: Biology and Bio-materials


Instruments: B21-High Throughput SAXS

Added On: 13/12/2021 09:56

Documents:
s42003-021-02887-4.pdf

Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Cancer Genetics Structural biology Life Sciences & Biotech

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)