Exploring the structural landscape of DNA maintenance proteins

Kenneth Bødkter Schou (), Samuel Mandacaru, Muhammad Tahir, Nikola Tom, Ann-Sofie Nilsson, Jens S. Andersen, Matteo Tiberti, Elena Papaleo and Jiri Bartek ()
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Kenneth Bødkter Schou: Danish Cancer Society
Samuel Mandacaru: University of Southern Denmark
Muhammad Tahir: University of Southern Denmark
Nikola Tom: Danish Cancer Institute (DCI)
Ann-Sofie Nilsson: Karolinska Institute
Jens S. Andersen: University of Southern Denmark
Matteo Tiberti: Danish Cancer Society Research Center
Elena Papaleo: Danish Cancer Society Research Center
Jiri Bartek: Danish Cancer Society

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Evolutionary annotation of genome maintenance (GM) proteins has conventionally been established by remote relationships within protein sequence databases. However, often no significant relationship can be established. Highly sensitive approaches to attain remote homologies based on iterative profile-to-profile methods have been developed. Still, these methods have not been systematically applied in the evolutionary annotation of GM proteins. Here, by applying profile-to-profile models, we systematically survey the repertoire of GM proteins from bacteria to man. We identify multiple GM protein candidates and annotate domains in numerous established GM proteins, among other PARP, OB-fold, Macro, TUDOR, SAP, BRCT, KU, MYB (SANT), and nuclease domains. We experimentally validate OB-fold and MIS18 (Yippee) domains in SPIDR and FAM72 protein families, respectively. Our results indicate that, surprisingly, despite the immense interest and long-term research efforts, the repertoire of genome stability caretakers is still not fully appreciated.

Date: 2024
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DOI: 10.1038/s41467-024-49983-7

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