DNA replication is an essential but a precarious cellular process of central importance both to the development of cancer and its treatment. Failure in the proper replication process generates replication stress that contribute to genome instability, an early event in tumorigenesis. Replication fork stability pathways mediate tolerance to replication stress which if adapted by cancer cells can lead to resistance towards replication stress inducing chemotherapeutic drugs.
Work in the Taneja lab (Chromatin Remodeling & Replication group)
, is focused on understanding the mechanisms modulating chromatin via chromatin modifiers to mediate stabilization of stressed replication forks in efforts towards the treatment as well as prevention of tumorigenesis. Recent work by us have discovered a novel mechanism of stabilizing "active replication forks" by ensuring chromatin remodeling activity of SWI/SNF remodeler (Lo et al. Science Advances, 2021; Uruci et al. IJMS, 2021). This process is critical for restart of stressed replication forks and to maintain replication-associated genome stability, especially in fork-protection challenged BRCA1-deficient tumor cells for their survival. In the current project, funded by NWO-Vidi grant, the PhD student will further dissect the enigmatic role of chromatin architecture organization mediated by chromatin remodeling activities in tolerating replication stress. The student will employ a multidisciplinary approaches of genetic, biochemistry, cellular and molecular biology combined with NextGen-Sequencing methodologies and involving novel technologies developed in the lab to explore the role of chromatin organization in modulating replication stress.