Interstrand DNA crosslink, molecular model. Crosslinking of DNA occurs when various exogenous or endogenous agents react with two nucleotides of DNA, forming a covalent linkage between them. This crosslink can occur within the same strand (intrastrand) or, as it is the case here, between opposite strands of double-stranded DNA (interstrand). Interstrand cross-links are exceptionally bioactive DNA lesions. Endogenous generation of interstrand cross-links in genomic DNA may contribute to aging, neurodegeneration, and cancer. If such a lesion undergoes spontaneous and amine-catalysed strand cleavage reactions, it is called an abasic site. Abasic (AP) sites are one of the most common forms of DNA damage.