TY - JOUR
T1 - Exploring the structural landscape of DNA maintenance proteins
AU - Schou, Kenneth Bødkter
AU - Mandacaru, Samuel
AU - Tahir, Muhammad
AU - Tom, Nikola
AU - Nilsson, Ann Sofie
AU - Andersen, Jens S.
AU - Tiberti, Matteo
AU - Papaleo, Elena
AU - Bartek, Jiri
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-024-49983-7
DO - 10.1038/s41467-024-49983-7
M3 - Journal article
C2 - 39237506
AN - SCOPUS:85203296234
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
M1 - 7748
ER -