Maintenance of genome stability and homologous recombination
The Esashi group aims to understand how proliferating human cells protect their genomic DNA against various environmental stresses (e.g., radiation, genotoxic drugs) as well as those arising from normal processes of cell growth (e.g., replication, transcription). We are particularly interested in homologous recombination (HR), which provides a powerful mechanism to repair broken DNA faithfully and therefore to maintain genome stability, but may conversely alter genomic information if it is engaged by mistake. We aim to answer the fundamental question: ‘how is HR activated at the right time and at the right location?’
Our previous studies revealed several unexpected regulatory mechanisms for HR, whereby the key HR proteins Rad51, BRCA2 and PALB2 are regulated spatio-temporally by central cell cycle kinases such as cyclin-dependent kinases (CDKs) and polo-like kinase 1 (Plk1) in proliferating human cells (Esashi et al., Nature, 2005; Esashi et al., NSMB, 2007; Yata et al., Mol Cell, 2012; Bleuyard et al., EMBO R, 2012; Yata et al., Cell Reports, 2014). The group continues to tackle challenging questions regarding the regulation of HR using a multidisciplinary approach, including molecular and cellular biology, bioimaging, proteomics, protein biochemistry, and mathematical modelling.