Abstract
Homologous recombination (HR) is essential for cells to maintain genome stability through the precise repair of DNA double-strand breaks and other lesions that are produced by a variety of exogenous and endogenous agents. Defects in HR due to mutations or epigenetic silencing of the HR genes are associated with cancer predisposition. We have recently found that meiosis-specific synaptonemal complex proteins are aberrantly expressed in various cancer cells, whereas their roles in mitotic cells are poorly understood. In this symposium, we will show that HR can be inactivated by aberrant expression of the meiosis-specific synaptonemal complex protein SYCP3 in mitotic cells, raising a novel mechanism for genome instability and cancer development. We generated epithelial cells expressing SYCP3, and found that these cells demonstrated phenotypes reflecting impaired HR, such as increased DNA double-strand breaks, hypersensitivity to DNA damage, reductions in radiation-induced RAD51 foci formation and sister chromatid exchanges, and aneuploidy. The molecular mechanism underlying the inhibition of HR by SYCP3 will be discussed based on our recent data on dynamics of SYCP3 and key molecules involved in HR.
