Putative gatekeepers of incoming DNA: 3′ exonucleases in natural transformation and bacterial evolution

Natural transformation is a key mechanism of bacterial adaptation in which exogenous DNA (eDNA) is taken up, processed into single-stranded DNA (ssDNA), and integrated into the genome. While earlier studies primarily focused on uptake mechanisms, transport proteins, and recombination processes, exonucleases were long regarded as merely nonspecific degradation enzymes in DNA uptake. However, recent studies show that nucleases, partly related to the SOS response, play a key role in processing uptake ssDNA. They affect the imported DNA, thereby promoting efficient recombination. This review highlights the interactions between nucleases and taken-up ssDNA, discusses the functional link between natural competence and the bacterial SOS damage response, and demonstrates that key components of these processes have been conserved in bacteria. This suggests a possible universal principle in which ssDNA-specific nucleases serve as switches between the DNA damage response, competence, and horizontal gene transfer.