In this section
@article{Faull:2025:10.1038/s41467-024-55479-1,
author = {Faull, S and Barbon, M and Mossler, A and Yuan, Z and Bai, L and Reuter, LM and Riera, A and Winkler, C and Magdalou, I and Peach, M and Li, H and Speck, C},
doi = {10.1038/s41467-024-55479-1},
journal = {Nature Communications},
title = {MCM2-7 ring closure involves the Mcm5 C-terminus and triggers Mcm4 ATP hydrolysis},
url = {http://dx.doi.org/10.1038/s41467-024-55479-1},
volume = {16},
year = {2025}
}
TY - JOUR
AB - The eukaryotic helicase MCM2-7, is loaded by ORC, Cdc6 and Cdt1 as a double-hexamer onto replication origins. The insertion of DNA into the helicase leads to partial MCM2-7 ring closure, while ATP hydrolysis is essential for consecutive steps in pre-replicative complex (pre-RC) assembly. Currently it is unknown how MCM2-7 ring closure and ATP-hydrolysis are controlled. A cryo-EM structure of an ORC-Cdc6-Cdt1-MCM2-7 intermediate shows a remodelled, fully-closed Mcm2/Mcm5 interface. The Mcm5 C-terminus (C5) contacts Orc3 and specifically recognises this closed ring. Interestingly, we found that normal helicase loading triggers Mcm4 ATP-hydrolysis, which in turn leads to reorganisation of the MCM2-7 complex and Cdt1 release. However, defective MCM2-7 ring closure, due to mutations at the Mcm2/Mcm5 interface, leads to MCM2-7 ring splitting and complex disassembly. As such we identify Mcm4 as the key ATPase in regulating pre-RC formation. Crucially, a stable Mcm2/Mcm5 interface is essential for productive ATP-hydrolysis-dependent remodelling of the helicase.
AU - Faull,S
AU - Barbon,M
AU - Mossler,A
AU - Yuan,Z
AU - Bai,L
AU - Reuter,LM
AU - Riera,A
AU - Winkler,C
AU - Magdalou,I
AU - Peach,M
AU - Li,H
AU - Speck,C
DO - 10.1038/s41467-024-55479-1
PY - 2025///
SN - 2041-1723
TI - MCM2-7 ring closure involves the Mcm5 C-terminus and triggers Mcm4 ATP hydrolysis
T2 - Nature Communications
UR - http://dx.doi.org/10.1038/s41467-024-55479-1
UR - https://www.nature.com/articles/s41467-024-55479-1
VL - 16
ER -