title: Synaptonemal complex protein SYCP3 impairs mitotic recombination by interfering with BRCA2.
abstract: 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.
authors: Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan. nhosoya-tky@umin.ac.jp
authors: Noriko
authors: N
authors: Hosoya
authors: Miyuki
authors: M
authors: Okajima
authors: Aiko
authors: A
authors: Kinomura
authors: Yoshihiro
authors: Y
authors: Fujii
authors: Takashi
authors: T
authors: Hiyama
authors: Jiying
authors: J
authors: Sun
authors: Satoshi
authors: S
authors: Tashiro
authors: Kiyoshi
authors: K
authors: Miyagawa
mesh_terms: D000782:Aneuploidy; D024682:BRCA2 Protein / Q000378:metabolism*; D018797:Cell Cycle Proteins; D043171:Chromosomal Instability; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects; D004268:DNA-Binding Proteins; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020868:Gene Silencing; D056945:Hep G2 Cells; D059765:Homologous Recombination; D006801:Humans; D008938:Mitosis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011485:Protein Binding; D051135:Rad51 Recombinase / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics; D012854:Sister Chromatid Exchange
chemical_list: D024682:BRCA2 Protein; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C490060:SYCP3 protein, human; D051135:Rad51 Recombinase