Sequencing abasic sites in DNA at single-nucleotide resolution

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Abasic sites, resulting from nucleobase loss via hydrolysis, are common DNA lesions.
• These sites are implicated in DNA damage, mutations, strand breaks, and base excision repair.
• Existing methods lack precision in resolving abasic sites from other DNA aldehydes.

Purpose of the Study:

• To introduce snAP-seq, a novel chemical approach for single-nucleotide resolution mapping of abasic sites.
• To differentiate abasic sites from other endogenous aldehyde functionalities in genomic DNA.
• To investigate the distribution of DNA lesions and modifications in different genomes.

Main Methods:

• Development of snAP-seq, a chemical strategy targeting the aldehyde moiety of abasic sites.
• Validation of snAP-seq on synthetic DNA constructs.
• Application of snAP-seq to map thymine modifications in *Leishmania major* and endogenous abasic sites in HeLa DNA.

Main Results:

• snAP-seq successfully maps abasic sites at single-nucleotide resolution.
• The method distinguishes abasic sites from other genomic aldehydes.
• Mapping revealed patterns of thymine modifications in *Leishmania major* and endogenous abasic sites in human DNA.

Conclusions:

• snAP-seq provides a powerful tool for precise abasic site detection and genomic analysis.
• This technique advances the study of DNA damage, repair pathways, and genome integrity.
• The findings offer insights into DNA lesion distribution in different species.