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bioRxiv · 10.1101/2021.07.24.453613

Refining the domain architecture model of the replication origin firing factor Treslin/TICRR

Ferreira, P.·Sanchez-Pulido, L.·Marko, A.·Ponting, C. P.·Boos, D.
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Abstract

Faithful genome duplication requires appropriately controlled replication origin firing. The metazoan Treslin/TICRR origin firing factor and its yeast orthologue Sld3 are regulation hubs of origin firing. They share the Sld3-Treslin domain (STD) and the adjacent TopBP1/Dpb11 interaction domain (TDIN). We report a revised domain architecture model of Treslin/TICRR. Complementary protein sequence analyses uncovered Ku70-homologous {beta}-barrel folds in the Treslin/TICRR middle domain (M domain) and in Sld3. Thus, the Sld3-homologous Treslin/TICRR core comprises its three central domains, M domain, STD and TDIN. This Sld3-core is flanked by non-conserved terminal domains, the CIT (conserved in Treslins) and the C-terminus. We also identified Ku70-like {beta}-barrels in MTBP and Sld7. Our binding experiments showed that the Treslin {beta}-barrel mediates interaction with the MTBP {beta}-barrel, reminiscent of the homotypic Ku70-Ku80 dimerization. This binding mode is conserved in the Sld3-Sld7 dimer. We used Treslin/TICRR domain mutants to show that all Sld3-core domains and the non-conserved terminal domains fulfil important functions during origin firing in human cells. Thus, metazoa-specific and widely conserved molecular processes cooperate during origin firing in metazoa.

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Ferreira, P., Sanchez-Pulido, L., Marko, A., Ponting, C. P., Boos, D.. 2021-07-24. Refining the domain architecture model of the replication origin firing factor Treslin/TICRR. https://doi.org/10.1101/2021.07.24.453613

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