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Nucleotide excision repair (NER) represents one of the major molecular machineries that control chromosome stability in all living species. In Eubacteria, the initial stages of the repair process are carried out by the UvrABC excinuclease complex. Despite the wealth of structural data available, some crucial details of the pathway remain elusive. In this study, we present a structural investigation of the Mycobacterium tuberculosis UvrAUvrB complex and of the UvrA dimer, both in complex with damaged DNA. Our analyses yield insights into the DNA binding mode of UvrA, showing an unexplored conformation of Insertion Domains (IDs), underlying the essential role of these domains in DNA coordination. Furthermore, we observe an interplay between the ID and the UvrB Binding Domain (UBD): after the recognition of the damage, the IDs repositions with the concomitant reorganization of UBD, allowing the formation of the complex between UvrA and UvrB. These events are detected along the formation of the uncharacterized UvrA2UvrB1-DNA and the UvrA2UvrB2-DNA complexes which we interpret as hierarchical steps initiating the DNA repair cascade in the NER pathway, resulting in the formation of the pre-incision complex. 

In computational physics, chemistry, and biology, the implementation of new techniques in shared and open-source software lowers barriers to entry and promotes rapid scientific progress. However, effectively training new software users presents several challenges. Common methods like direct knowledge transfer and in-person workshops are limited in reach and comprehensiveness. Furthermore, while the COVID-19 pandemic highlighted the benefits of online training, traditional online tutorials can quickly become outdated and may not cover all the software’s functionalities. To address these issues, here we introduce “PLUMED Tutorials,” a collaborative model for developing, sharing, and updating online tutorials. This initiative utilizes repository management and continuous integration to ensure compatibility with software updates. Moreover, the tutorials are interconnected to form a structured learning path and are enriched with automatic annotations to provide broader context. This paper illustrates the development, features, and advantages of PLUMED Tutorials, aiming to foster an open community for creating and sharing educational resources.