Ans: Double-strand breaks or DSBs can be caused by IR which is either directly through radical and ionization attacks or indirectly when base damages occur close to the Single strand breaks or on the opposite  DNA strand. This damage which is related to IR is also called clustered damage. A double-strand break can also occur due to the body’s own metabolic activities like reactive oxygen species which can result in the blockage of the progression of DNA replication. The detection, signalling, and repair of DSBs need an extensive cellular response which is called DDR or DNA damage response. For DDR to happen, the ATM kinase (a member of PI3K or phosphoinositide 3-kinase protein family) needs to be activated which is then recruited to chromatin to correct DSBs by interacting with the MRN complex. After this interaction, a signalling cascade happens due to the phosphorylation of a huge number of substrates. This signalling then activates checkpoints in the cell cycle to recruit repair factors to the damaged site.