Mutational signatures

Mutational Signatures

Identification of Mutational Signatures

Mutational signatures are unique patterns of mutations that arise in the DNA of cells due to various endogenous and exogenous processes. These signatures are crucial for understanding the underlying mechanisms of carcinogenesis and other genetic disorders. By analyzing these patterns, researchers can infer the history of mutational processes that have acted on a genome.

Types of Mutations

Types of Mutations

Mutations can be broadly categorized into several types, including single base substitutions, insertions and deletions, and larger structural variations. Each type of mutation can contribute to a distinct mutational signature. For example, single base substitutions are often categorized into six types based on the substitution of one base for another, such as C>T or G>A transitions.

Mechanisms of Mutational Signatures

Mutational signatures can arise from a variety of mechanisms:

• Endogenous processes: These include spontaneous deamination of cytosine to uracil, errors during DNA replication, and the activity of DNA repair pathways such as base excision repair (BER).

• Exogenous factors: Environmental factors such as ultraviolet radiation, tobacco smoke, and chemotherapy agents can induce specific mutational patterns.

Base Excision Repair and Mutational Signatures

Base Excision Repair Pathway

The base excision repair (BER) pathway is a critical mechanism for repairing small base lesions in DNA. Defects in this pathway can lead to characteristic mutational signatures. For instance, mutations in the MUTYH gene, which is involved in BER, can result in a specific signature associated with colorectal cancer.

Applications of Mutational Signatures

Understanding mutational signatures has several important applications:

• Cancer research: By identifying the mutational signatures present in a tumor, researchers can infer the mutagenic processes that contributed to its development. This can inform treatment strategies and identify potential therapeutic targets.

• Genetic disease: Mutational signatures can also provide insights into the etiology of genetic disorders, helping to identify the underlying genetic defects and their consequences.

• Evolutionary biology: Studying mutational signatures across different species can shed light on evolutionary processes and the impact of environmental factors on genetic variation.

Related Pages

• DNA repair
• Carcinogenesis
• Genetic mutation
• Cancer genomics