DNA encodes the genetic information, it is crucial to maintain its integrity during replication to pass the right genetic information in newly formed cells but world is not perfect, now and then DNA is constantly abused by the environmental agents and endogenous free radical generated inside the cells that damage the sugar and base. These accumulated errors in the DNA may result in cancer or apoptosis. Nature has evolved highly specialized polymerases to repair or bypass the lesions at the stalled site of DNA replication. Once the lesion is generated in the DNA, the replication machine stall, now either the lesion is repaired or bypass by specialized polymerases. Proliferating cell nuclear antigen (PCNA) plays instrumental role in translesion synthesis (TLS) by providing the platform to TLS polymerases for efficient bypass of the lesions. In normal scenario DNA is replicated by polymerase delta bound to PCNA and other accessory proteins. At the site of lesion, replication is stalled and PCNA is ubiquitinated by RAD6/RAD18 proteins dependant manner and polymerase delta is replaced by pol h. We are interested in studying the underlying mechanism of polymerase switch and the coordination of proteins involved in TLS. The two possible ways of polymerase switch during TLS are illustrated in the following animations.

Our major efforts in this cutting edge research involve the use of Biochemical, Biophysical and Molecular Biology approaches such as steady-state, presteady-state kinetic, isothermal titration calorimetry (ITC), cross-linking, analytical ultracentrifugation, surface plasmon resonance (SPR), tandem mass spectrometry, fluorescence resonance energy transfer (FRET),single molecule FRET and protein expression & purification (E. coli, Yeast, insect and human cells) to better understand TLS process.