Evidence for strong interplay between the nucleotide and base excision repair pathways in D. radiodurans
Year: 2026
Type: preprint
Abstract: ABSTRACT Deinococcus radiodurans harbors a largely classical bacterial DNA repair machinery yet displays exceptional resistance to ultra-violet and ionizing radiation. To investigate whether crosstalk between its DNA repair pathways contributes to this phenotype, we mapped putative interactions between the nucleotide excision repair (NER) and base excision repair (BER) pathways, which together are responsible for the removal of nucleobase lesions. Using a bacterial two-hybrid system, we identified multiple direct interactions between NER and BER proteins, notably involving the two UvrA variants, and validated these interactions in vitro . Furthermore, functional analyses revealed that NER interferes with the BER-mediated removal of oxidized guanines by the Fpg DNA glycosylase, likely through competition for DNA binding and sequestration of Fpg. Finally, UvrB and UvrC were found to further process the Fpg incision product in an ATP-dependent, UvrA1-independent manner. Together, these results demonstrate a multi-level crosstalk between NER and BER in D. radiodurans , which may contribute to its extraordinary DNA repair capacity. To our knowledge, this represents the first evidence of such a complex interplay in bacteria.
Institutions: Centre National de la Recherche Scientifique, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, CEA Grenoble, Institut de Biologie Structurale, Systèmes Moléculaires et nanoMatériaux pour l'Énergie et la Santé, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7164012771