APOBEC mutagenesis is low in most types of non-B DNA structures

Area of Science:

• Genomics
• Molecular Biology
• Cancer Research

Background:

• Somatic mutations are known to associate with non-canonical DNA structures.
• The specific influence of mutagens on these associations requires further investigation.

Purpose of the Study:

• To elucidate the impact of APOBEC mutagenesis on various DNA secondary structures in human cancers.
• To investigate the distribution of APOBEC and UV mutagenesis across different DNA forms.

Main Methods:

• Analysis of mutation patterns in human cancer genomes.
• Comparison of mutation densities in B-DNA, G-quadruplexes, inverted repeats, and Z-DNA.
• Assessment of APOBEC activity levels and their correlation with mutation sites.

Main Results:

• APOBEC mutagenesis is not enriched in direct repeats, mirror repeats, short tandem repeats, or G-quadruplexes, and is reduced in B-DNA at high APOBEC activity.
• APOBEC-induced mutations are positively associated with APOBEC activity in inverted repeats (cruciform structures).
• APOBEC mutagenesis and UV mutagenesis in melanoma are absent in Z-DNA regions.

Conclusions:

• APOBEC mutagenesis distribution is structure-dependent and influenced by DNA secondary structures.
• Inverted repeats are hotspots for APOBEC-induced mutations, while Z-DNA regions are protected from both APOBEC and UV mutagenesis.