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Proliferation of all cells hinges upon faithful duplication and equal distribution of the genetic material. In human cells, the duplication of genetic materials is orchestrated by DNA replication machinery, which needs to accurately copy more than 6 billion base pairs during each cell division cycle. This is a formidable endeavor considering that nearly 2 meters of DNA per cell is compacted into a nucleus with a diameter of less than 10 μm. If that alone were not sufficiently daunting, DNA replication must also cope with myriad obstacles to the progression of the replication machinery, such as DNA lesions triggered by the byproduct of cell metabolism (reactive oxygen) or exposure to genotoxic agents (e.g., UV radiation, chemical mutagens).

Cells have evolved intricate pathways to repair damaged DNA. Coordination of DNA replication with DNA-damage sensing/repair and cell-cycle progression ensures genome integrity and promotes faithful genome propagation. Aberrations in any of these sophisticated machineries or pathways lead to genetic anomalies ranging from point mutations to chromosome rearrangements to gain or loss of part or whole chromosome. This increased tendency of genome alteration during cell division is referred to as genome instability. Although such events can be harmful to the cell and the organism, they also drive evolution at the molecular level and generate genetic variation. Genomic instability is a hallmark of cancers; it enables cancer cells to evolve and provide an adaptive advantage to cope with several different problems that arise with continuous proliferation, a primary characteristic of cancer cells.

Our laboratory is dedicated to unraveling the molecular intricacies underpinning the maintenance of genome stability, deciphering how cancer cells subvert these mechanisms, and devising innovative strategies to target these vulnerabilities. Ultimately, we endeavor to pioneer transformative approaches in cancer therapeutics, advancing the frontiers of scientific understanding and clinical intervention.