Cell division cycle in eukaryotes is a critical and highly regulated process. Any deregulation in the cellular process may result in uncontrolled cell proliferation and genomic instability leading to various diseases including cancer. The regulatory mechanisms include modulation of differential abundance and activities of gene products controlling their interaction among themselves and with genome. In this context, the research activities in the laboratory focus primarily on the mechanisms regulating various cellular processes during cell cycle progression in mammalian system.
Regulation of gene expression at post-transcriptional level in eukaryotes: In addition to the regulation at transcriptional level, post-transcriptional mechanisms are also critical determinant of the differential proteomes affecting cell phenotypes. Post-transcriptional regulation primarily depends on the controlled interaction between the cis-elements on mRNA and trans-factors including proteins and micro-RNAs. Such interactions regulate the mRNA turnover and translation during key physiological and pathological processes to modulate the abundances of gene products in cells. Deregulation of such processes involving mRNAs encoding proteins including cell cycle regulators and growth factors correlates with several pathological conditions like cancer. In this context, we are interested to elucidate the role of cis-elements in the UTR of mRNAs of several mammalian cell cycle related genes at molecular and cellular level using various techniques of cell and molecular biology and high-throughput approaches such as next generation sequencing and proteome analysis.
Crosstalk between replication and repair: Accurate replication of DNA in eukaryotic cells is controlled by a cell cycle dependent licensing mechanism that allows formation of a competent pre-replication complex only after mitotic segregation of sister chromatids into daughter cells. Intriguingly, Ku – a DNA repair protein is also involved in the process but its regulation remained long unknown. It has already been shown in our laboratory using one human origin that the periodic modulation of replication related function of Ku is dependent on reversible phosphorylation of its Ku70 subunit by cell cycle kinases (Accepted for publication, Nucleic Acid Research, 2016). Since the critical process of replication initiation during S-phase is regulated in a spatiotemporal manner, the role of Ku in genome wide uses of thousands of origins will be elucidated via high throughput approaches like ChIP-seq. Our preliminary studies also implicate interesting functional interaction between the multi-functional Ku protein with cell cycle checkpoint pathways, and we are interested to explore that further in detail. Future research will focus to elucidate the critical regulatory link among replication initiation, checkpoint pathways and repair process in greater details. The effect of perturbation by various external agents on these processes will also be studied to understand the disease processes involving deregulation of cell proliferation. |
