Double-Strand Breaks in DNA: A Central Feature of Genomic Un-Stability Double-strand breaks (DSBs) are highly toxic forms of damage to chromosomal DNA. If such breaks are left unrepaired, devastating consequences such as cell death and genomic instability can arise. Unrepaired DSBs have a wide range of effects. These include:
Cellular Consequences
If the DSBs are not repaired it can be detected and cells that are unable to do so resolve to activate apoptosis, a cellular suicide signaling initiative of dealing with unrepairable harm to their genome. This cellular action is essential in controlling the spread of defective DNA that may promote oncogenic mutations.
Genomic Instability
Misrepaired DSBs can cause genomic rearrangements like deletions, translocations and fusions. Disrupting gene function and regulatory pathways, in some cases leading to cancer. For example, a variety of cancers are characterized by chromosomal translocations that result from mistakes in the mechanisms that rejoin chromosome ends after they have been broken.
Cancer Development
In cancer cells, the mistake repair of DSBs is abundant in nearly all cases. This is because these cells tend to experience more DSBs, which result from replication stress, and impaired DNA damage response mechanisms. In aggregate, genomic rearrangements may generate oncogenic mutations that contribute to tumorigenesis. Cancer cells can also use increased DSB repair capacity to withstand treatments as those based on radiation and chemotherapy, which in turn increases intra-tumor heterogeneity of resulting tumors and hampers therapeutic responses.
To sum up, the inability to repair DSB may influence cellular health and genomic stability, eventually making it more likely that cells will develop and progress into a cancer state.