Human genome is continuously damaged by environmental, exogenous/endogenous agents. The toxic effects of these factors cause lesions in DNA that have immediate effect on cell function as well as long-term consequences. Different toxicants induce cellular toxicity, for example toxicants such as alkylating agents induces genotoxic stress through modification of dNTPs and hence cause mutations and deletions in chromosomes resulting in genome instability. Genomic integrity is essential for accurate gene expression and epigenetic inheritance. To counteract the deleterious effects of DNA lesions cells have developed sophisticated genome caretaking mechanisms to overcome damage to DNA resulting in double-strand breaks (DSBs) induced by toxic agents through specialized network of DNA repair pathways regulated by DNA damage checkpoint proteins. These apical DNA damage checkpoint proteins regulate integrity of chromosomes through coordination of the cell cycle progression with DNA repair, DNA replication and recombination processes through induction of the DNA damage response (DDR). Improper repair of DSBs can lead to various developmental defects and become genesis of many modern diseases. Overall, we aim to study how cells respond to DNA damage and in addition understanding the mechanistic insights of how are distinct cellular processes coordinated in time to full restoration of genome integrity.