Genomic instability refers to an elevated tendency for mutations to occur within the genome of a cellular lineage. It’s a hallmark of many cancers and some other diseases, and it can also contribute to aging.
Genomic instability can occur in several forms:
- Point mutations: These are small-scale changes that affect only a few base pairs within the DNA sequence. They can lead to the production of defective proteins that can disrupt cellular functions.
- Chromosomal instability: This refers to changes in the number or structure of chromosomes, such as deletions, duplications, translocations, or aneuploidy (an abnormal number of chromosomes). These changes can have major effects on gene expression and function.
- Microsatellite instability: Microsatellites are short, repeated sequences of DNA. If the mechanisms for repairing errors in DNA replication are faulty, the length of these microsatellites can change, which can lead to mutations and disease.
- Replication stress: This is a condition in which the replication machinery is slowed or stalled, leading to incomplete or faulty DNA replication, which in turn can cause DNA damage and genomic instability.
Genomic instability can be caused by a variety of factors, including exposure to radiation or certain chemicals, errors in DNA replication or repair, and oxidative stress. Cells have several mechanisms to protect against genomic instability, including DNA repair mechanisms and cell cycle checkpoints that can halt the cell cycle to allow time for repair. However, if these mechanisms fail, genomic instability can result, leading to disease and aging.
In cancer, genomic instability can facilitate the evolution and adaptation of cancer cells, promoting tumor growth and resistance to therapy. On the other hand, it also provides potential targets for cancer therapy, as cancer cells often depend on certain DNA repair pathways to survive.
