Synaptonemal complex protein SYCP3 impairs mitotic recombination by interfering with BRCA2

The meiosis-specific synaptonemal complex protein SYCP3 has been reported to be aberrantly expressed in tumours. However, in contrast to its well-defined function in meiosis, its possible role in mitotic cells is entirely unknown. Here, we show that SYCP3 is expressed in a range of primary tumours a...

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Detalles Bibliográficos
Autores principales: Hosoya, Noriko, Okajima, Miyuki, Kinomura, Aiko, Fujii, Yoshihiro, Hiyama, Takashi, Sun, Jiying, Tashiro, Satoshi, Miyagawa, Kiyoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: European Molecular Biology Organization 2012
Materias:
Scientific Reports
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246250/
https://www.ncbi.nlm.nih.gov/pubmed/22116401
http://dx.doi.org/10.1038/embor.2011.221
Descripción
Sumario:The meiosis-specific synaptonemal complex protein SYCP3 has been reported to be aberrantly expressed in tumours. However, in contrast to its well-defined function in meiosis, its possible role in mitotic cells is entirely unknown. Here, we show that SYCP3 is expressed in a range of primary tumours and that it impairs chromosomal integrity in mitotic cells. Expression of SYCP3 inhibits the homologous recombination (HR) pathway mediated by RAD51, inducing hypersensitivity to DNA-damaging agents such as a poly(ADP-ribose) polymerase (PARP) inhibitor and chromosomal instability. SYCP3 forms a complex with BRCA2 and inhibits its role in HR. These findings highlight a new mechanism for chromosomal instability in cancer and extend the range of PARP-inhibitor sensitive tumours to those expressing SYCP3.

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