A conserved mechanism for regulating replisome disassembly in eukaryotes
Open accessAbstract
Replisome disassembly is the final step of eukaryotic DNA replication and is triggered by ubiquitylation of the CDC45–MCM–GINS (CMG) replicative helicase 1–3 . Despite being driven by evolutionarily diverse E3 ubiquitin ligases in different eukaryotes (SCF Dia2 in budding yeast 1 , CUL2 LRR1 in metazoa 4–7 ), replisome disassembly is governed by a common regulatory principle, in which ubiquitylation of CMG is suppressed before replication termination, to prevent replication fork collapse. Recent evidence suggests that this suppression is mediated by replication fork DNA 8–10 . However, it is unknown how SCF Dia2 and CUL2 LRR1 discriminate terminated from elongating replisomes, to selectively ubiquitylate CMG only after termination. Here we used cryo-electron microscopy to solve high-resolution structures of budding yeast and human replisome–E3 ligase assemblies. Our structures show that the leucine-rich repeat domains of Dia2 and LRR1 are structurally distinct, but bind to a common site on CMG, including the MCM3 and MCM5 zinc-finger domains. The LRR–MCM interaction is essential for replisome disassembly and, crucially, is occluded by the excluded DNA strand at replication forks, establishing the structural basis for the suppression of CMG ubiquitylation before termination. Our results elucidate a conserved mechanism for the regulation of replisome disassembly in eukaryotes, and reveal a previously unanticipated role for DNA in preserving replisome integrity.
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In budding yeast, previous experiments mapped the POLD3-POLA1 interaction to the location in both proteins predicted by AF-M.
“in budding yeast, previous experiments mapped this interaction to the location in both proteins predicted by AF-M69,70.”
From Predictomes, a classifier-curated database of AlphaFold-modeled protein-protein interactions (2025) · cites this paper as [69]
The Terminated yeast replisome structures section describes Pol-ε and a Dia2–CMG interface, while the Dia2LRR–MCM interface section reports experiments on that interface. Neither addresses a POLD3–POLA1 interaction or compares its experimentally mapped location with an AF-M prediction. Searches for POLD3, POLA1, and the yeast protein names Pol32 and Pol1 found no relevant passage; page numbers were unavailable in our copy. (LLM, conf=0.76)
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CDK-driven phosphorylation of TRAIP is essential for mitotic replisome disassembly and MiDAS
Poovathumkadavil, D., Reynolds-Winczura, A., Skagia, A., Passaretti, P., Sadurnì, M. M., Kingsley, G., Leitner, A., Saponaro, M., & Gambus, A. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf530 · Cited by 9 · see citing works
“No interactions of TRAIP with TIMELESS and TIPIN, which are positioned at the utter most forward-facing end of the replisome [ 24 ], have been re-ported thus far .”
Embracing Heterogeneity: Challenging the Paradigm of Replisomes as Deterministic Machines
Lewis, J. S., van Oijen, A. V., & Spenkelink, L. M. (2023) · Chemical Reviews · doi:10.1021/acs.chemrev.3c00436 · Cited by 9 · see citing works
DNA Damage Repair-Related Genes Signature for Immune Infiltration and Outcome in Cervical Cancer
Wang, X.-H., Xu, C., & Sun, H.-Z. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.733164 · Cited by 9
CMG helicase disassembly is essential and driven by two pathways in budding yeast
Rivera, C. P., Deegan, T., & Labib, K. P. M. (2024) · bioRxiv · doi:10.1038/s44318-024-00161-x · Cited by 8
“Structure-guided mutations in the leucine-rich repeats of Dia2, which bind to the Mcm2 – 7 component of CMG (Jenkyn-Bedford et al, 2021), phenocopy the CMG disassembly and cold-sensitivity phenotypes of dia2 Δ cells (Jenkyn-Bedford et al, 2021).”
InfluentialSelf-citationDegrons and degradation signals beyond short linear motifs
Wang, B., & Zheng, N. (2025) · Nature Chemical Biology · doi:10.1038/s41589-025-02056-2 · Cited by 8 · see citing works
“Such a multifaceted interface is best exemplified by the interaction between the terminated replisome and the yeast SCF Dia2 E3, as well as its mammalian counterpart CRL2 LRR1 , both of which ubiquitinate the Mcm7 subunit 54 (Fig.”
A Decade of Discovery—Eukaryotic Replisome Disassembly at Replication Termination
Jones, R. M., Reynolds-Winczura, A., & Gambus, A. (2024) · Biology · doi:10.3390/biology13040233 · Cited by 7 · see citing works
“In answer to this, cryoEM structures of the yeast and human terminated replisomes in complex with the ubiquitin ligase revealed an elongated arm extending from the N-tier of the MCM2-7 helicase [74].”
BackgroundInfluentialTang, Y., Li, Q.-F., Zhang, D., Ma, Z.-J., Yang, J., Cui, Y., & Zhang, A. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.977156 · Cited by 7 · see citing works
“Recent studies have also shown that CDC45 regulated MCM7 in acute myeloid leukemia through the PI3K/AKT pathway, and another mechanism whereby replication partially disrupted eukaryotic DNA replication and triggered by ubiquitination of replication helicases (Zhang et al., 2021b; Jenkyn-Bedford et al., 2021).”
BackgroundYan, J., Zhang, Z., Ge, Y.-X., Chen, J.-R., Gao, Y., & Zhang, B.-L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252011311 · Cited by 6 · see citing works
“CDCA5 and CDC45 are both cell-division cycle-associated proteins that are related to chromatin-binding activity [24] and essential for initiating DNA replication [25–27] and also play an important role in DNA repair [28].”
BackgroundA common mechanism for recruiting the Rrm3 and RTEL1 accessory helicases to the eukaryotic replisome
Olson, O., Pelliciari, S., Heron, E. D., & Deegan, T. (2024) · EMBO Journal · doi:10.1038/s44318-024-00168-4 · Cited by 6 · see citing works
“Docking of the Rrm3-Sld5 and Rrm3-Dpb2 AlphaFold-Multimer models onto a structure of the budding yeast replisome (Jenkyn-Bedford et al, 2021) revealed two important features of the predicted Rrm3-CMGE interface (Fig.”
Self-citationMicolucci, L., Matacchione, G., Albertini, M. C., Marra, M., Ramini, D., Giuliani, A., Sabbatinelli, J., Procopio, A. D., Olivieri, F., Marsico, A., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065123 · Cited by 8 · see citing works
USP37 prevents premature disassembly of stressed replisomes by TRAIP
Kochenova, O. V., D’Alessandro, G., Pilger, D., Schmid, E., Richards, S. L., Garcia, M. R., Jhujh, S. S., Voigt, A., Gupta, V., Carnie, C. J., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60139-z · Cited by 6 · see citing works
“However, because CRL2 Lrr1 is thought to be recruited to CMGs that have completed DNA replication, this hyper-ubiquitylation is unlikely to be deleterious 8,9 .”
InfluentialUSP37 prevents unscheduled replisome unloading through MCM complex deubiquitination
Bolhuis, D. L., Fleifel, D., Bonacci, T., Wang, X.-X., Mouery, B. L., Cook, J. G., Brown, N. G., & Emanuele, M. J. (2025) · Nature Communications · doi:10.1038/s41467-025-59770-7 · Cited by 5 · see citing works
“All references to Figures and manuscript lines are to those in this revised submission.”
Competition for the nascent leading strand shapes the requirements for PCNA loading in the replisome
Fletcher, E. E., Jones, M. L., & Yeeles, J. T. P. (2025) · EMBO Journal · doi:10.1038/s44318-025-00386-4 · Cited by 5 · see citing works
“In a human replisome reconstruction, POLE1 cat was rigidly associated with the non-catalytic domain such that the active site was situated ~140 Å from where the unwound leading-strand template emerges from the pore of CMG (Jones et al, 2021).”
InfluentialSelf-citationXiang, S., Craig, K. C., Luo, X., Welch, D. L., Ferreira, R. B., Lawrence, H. R., Lawrence, N. J., Reed, D. R., & Alexandrow, M. (2024) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-23-0904 · Cited by 5
“A possible explanation is that in vivo other factors may contribute to replisome disassembly, such as the ubiquitin ligase CUL2(LRR1), which contributes to disassembly (50).”
BackgroundControl of DNA replication in vitro using a reversible replication barrier
Vontalge, E. J., Kavlashvili, T., Dahmen, S. N., Cranford, M., & Dewar, J. M. (2024) · Nature Protocols · doi:10.1038/s41596-024-00977-1 · Cited by 5
The novel peptide PFAP1 promotes primordial follicle activation by binding to MCM5
Zhang, Y., Wang, H., Zhu, Y., Hou, X.-J., Li, X., Zhou, X., Ge, L., Xu, J.-Y., & Su, Y.-P. (2023) · The FASEB Journal · doi:10.1096/fj.202201495rr · Cited by 5
Lai, T.-Q., Peng, T., Li, J.-Y., Jiang, Y.-C., Liu, K., Yu, W., Yao, N., Hu, Y., Cao, M.-R., & Liang, J. (2023) · Translational Cancer Research · doi:10.21037/tcr-22-2565 · Cited by 5 · see citing works
Structure of the pre-initiation complex explains CMGE biogenesis
Pühringer, T., Canal, B., Palm, G., Butryn, A., Couves, E. C., Willhoft, O., Lewis, J. S., Diffley, J., & Costa, A. (2026) · bioRxiv · doi:10.1038/s41586-026-10657-7 · Cited by 4 · see citing works
“7 and 8 and Extended Data Table 2), or in sCMGE at termination 48 .”
Kumar, H., & Sobhia, M. E. (2026) · Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.5c07053 · Cited by 4 · see citing works
Ubiquitin and SUMO pathways in DNA replication and replication-coupled repair
Fiedorowicz, L., Baxley, R. M., Hendrickson, E. A., & Bielinsky, A. (2025) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2025.2574638 · Cited by 4 · see citing works
“, where lagging strand DNA exits the cMG complex. this steric interaction prevents premature cMG ubiquitination and disassembly (Jenkyn-Bedford et al. 2021; le et al. 2021; Zhou et al. 2021). loss of lrr1 impairs replisome disassembly and triggers AtR-mediated checkpoint activation (Fan et al.…”
Evolution of cullin E3 ubiquitin ligases and function in trypanosomesPreprint
del Pino, R. C., Zoltner, M., Yamada, K., Butterfield, E. R., & Field, M. C. (2023) · bioRxiv · doi:10.1101/2023.07.24.550360 · Cited by 4 · see citing works
“Significantly, the anaphase promoting complex (APC) and replisome also contain a cullin/ Rbx ubiquitin ligase at their core and govern turnover of critical proteins during mitosis (Alfieri et al., 2017, Jenkyn-Bedford et al., 2021).”
BackgroundUSP37 prevents premature disassembly of stressed replisomes by TRAIP
Kochenova, O. V., D’Alessandro, G., Pilger, D., Schmid, E., Richards, S. L., Garcia, M. R., Jhujh, S. S., Voigt, A., Gupta, V., Carnie, C. J., et al. (2024) · doi:10.1101/2024.09.03.611025 · Cited by 3 · see citing works
Zhang, Z., Zhang, S.-Y., Guo, L., Pan, Y., Huang, J., Ji, Y., Tao, J., Wei, Y., Wang, X., & Wu, Q. (2025) · Advancement of science · doi:10.1002/advs.202505787 · Cited by 3 · see citing works
Xiong, H., Wang, D., Fan, Y., Zhang, Y.-J., Ma, Q., Wei, Y.-L., Liang, M.-Q., & Xu, H.-G. (2025) · Animal Nutrition · doi:10.1016/j.aninu.2025.09.009 · Cited by 3
Matsuhashi, K., Ito, K. K., Nagai, K., Sanada, A., Watanabe, K., Takumi, K., Toyoda, A., Fukuyama, M., Yamamoto, S., Chinen, T., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-63002-3 · Cited by 3 · see citing works
“Consistent with this, the C-terminus of Cul2 and RBX1 can be predicted to be in close proximity to the primary ubi-quitylation sites on MCM7 (Fig.”
InfluentialUSP37 protects mammalian cells during DNA replication stress by counteracting CUL2LRR1 and TRAIP.
Villa, F., Ainsworth, J., & Labib, K. P. M. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115739 · Cited by 3 · see citing works
Self-citationThe non-catalytic ε DNA polymerase subunit is an NPF motif recognition protein
Keskitalo, S., Zámbó, B., Tuhkala, A., Salokas, K., Turunen, T., Deutsch, N., Davey, N., Dosztányi, Z., Varjosalo, M., & Gógl, G. (2025) · bioRxiv · doi:10.1101/2025.03.17.643635 · Cited by 3 · see citing works
Mechanism of DNA-protein crosslink bypass by CMG helicasePreprint
Kyaw, M., Xie, S., Peitz, E. D. L., & Yardimci, H. (2025) · bioRxiv · doi:10.1101/2025.03.06.641852 · Cited by 3 · see citing works
“Previous structural studies have identified an interaction between the CMG helicase and the excluded DNA strand at the replication fork, which has been suggested to shield the helicase from ubiquitination and disassembly during fork progression [22, 25, 50].”
Characterizing replisome disassembly in human cells
Jones, R. M., Ruiz, J. H., Scaramuzza, S., Nath, S., Liu, C.-Y., Henklewska, M., Natsume, T., Bristow, R., Romero, F., Kanemaki, M. T., et al. (2024) · iScience · doi:10.1016/j.isci.2024.110260 · Cited by 3 · see citing works
Structure and dynamics of a pentameric KCTD5/Cullin3/Gβγ E3 ubiquitin ligase complexPreprint
Nguyen, D. M., Rath, D. H., Devost, D., Pétrin, D., Rizk, R., Ji, A. X., Narayanan, N., Yong, D., Zhai, A., Kuntz, D. A., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.20.558662 · Cited by 4 · see citing works
“CRLs ubiquitylate a wide variety of substrates, ranging from intrinsically disordered proteins anchored via short degron motifs to ordered targets (for example, (30–33)).”
BackgroundImplications of ubiquitination and the maintenance of replication fork stability in cancer therapy
Xia, D., Zhu, X., Wang, Y., Gong, P., Su, H.-S., & Xu, X. (2023) · Bioscience Reports · doi:10.1042/bsr20222591 · Cited by 3 · see citing works
“The leucine-rich repeat domains of Dia2 and LRR1 bind to the zinc-finger domains of MCM3 and MCM5 within the CMG complex, but this interaction is occluded by the excluded DNA strand at replication forks before termination [59].”
BackgroundDeletions of DNA in cancer and their possible uses for therapy
Varshavsky, A., Lewis, K., & Chen, S.-J. (2023) · Bioessays · doi:10.1002/bies.202300051 · Cited by 3
Visualizing the Dynamics of DNA Replication and Repair at the Single-Molecule Molecule LevelPreprint
Berger, S. E., & Chistol, G. (2022) · bioRxiv · doi:10.1101/2022.10.22.513350 · Cited by 3 · see citing works
“It was discovered that during replication termination, a E3 ubiquitin ligase (ScfDia2 in yeast and CUL2LRR1 in vertebrates) poly-ubiquitylates the Mcm7 subunit of the CMG helicase, which is subsequently extracted from chromatin by p97/VCP (Fig.”
ResultFunctional insights into fungal F-box protein: From pathogenesis to sustainable economy
Pal, S., Shree, A., & Verma, P. K. (2024) · Fungal Biology Reviews · doi:10.1016/j.fbr.2024.100368 · Cited by 3
Mcm10 braces converging replicative helicases to pull apart origin DNAPreprint
Palm, G., Butryn, A., Canal, B., Pühringer, T., Gross, M. H., Diffley, J., & Costa, A. (2026) · bioRxiv · doi:10.64898/2026.05.15.725099 · Cited by 2 · see citing works
Template-driven scaffolding of SCFFBXO42 regulates PP2A degradation
Coassolo, S., Michaelian, N., Maculins, T., Azumaya, C. M., Cheung, T. K., Yin, J., Zilberleyb, I., Pahuja, K. B., Garner, T. P., Lau, T., et al. (2026) · Nature · doi:10.1038/s41586-026-10368-z · Cited by 3 · see citing works
“This concept is distinct from an adapter model in which E3 and the adapter form a composite interface to recruit substrates, and distinct from the binding of obligate protein complexes 45,46 .”
Xing, R., Lei, L., Fan, Z., Wang, L., Luo, L., Huang, Y.-Q., Zhang, H.-Y., Feng, Z., Chen, W., & Si, X. (2025) · Poultry Science · doi:10.1016/j.psj.2025.106253 · Cited by 2 · see citing works
Koit, S., Tamberg, N., Reinapae, A., Peil, L., Kristjuhan, A., & Ilves, I. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.108408 · Cited by 2 · see citing works
FADD Functions as an Oncogene in Chr11q13.3-Amplified Head and Neck Squamous Cell Carcinoma.
Zheng, Y., Chen, Y.-N., Meng, X.-Y., Zhang, L., Ma, Y.-N., Zhou, R., Fu, S.-T., Chen, H., Xuanyuan, X., Jiang, R., et al. (2025) · Cancer Research · doi:10.1158/0008-5472.can-24-2562 · Cited by 2
Steinkellner, H., Madritsch, S., Kluge, M., Seipel, T., Sarne, V., Huber, A., Schosserer, M., Oberle, R., Neuhaus, W., Beribisky, A. V., et al. (2024) · Genes · doi:10.3390/genes15121514 · Cited by 2 · see citing works
Prognostic importance of splicing-triggered aberrations of protein complex interfaces in cancer
Newaz, K., Schaefers, C., Weisel, K., Baumbach, J., & Frishman, D. (2024) · bioRxiv · doi:10.1093/nargab/lqae133 · Cited by 2 · see citing works
“The GINS complex has four protein subunits and helps in initiation and progression of DNA replication ( 45 ).”
BackgroundXiang, S., Luo, X., Welch, D., Reed, D., & Alexandrow, M. (2023) · Research Square · doi:10.21203/rs.3.rs-3182731/v1 · Cited by 2
Characterising replisome disassembly in human cells
Jones, R. M., Ruiz, J. H., Scaramuzza, S., Nath, S., Henklewska, M., Natsume, T., Romero, F., Kanemaki, M. T., & Gambus, A. (2022) · bioRxiv · doi:10.1101/2022.07.12.499744 · Cited by 2
“4 CUL2 can specifically recognise terminated helicases, as its substrate binding requires availability of an interaction surface on the CMG helicase, which is obscured by the excluded lagging strand ssDNA protruding from CMG during unwinding at replication forks (7-9).”
BackgroundMCM10 targets CMG dimers via a conserved mechanism for synchronized helicase activationPreprint
Taylor-Cross, E., Jones, M. L., Roske, J. J., Fletcher, E. E., Chan, I. X. R., & Yeeles, J. T. P. (2026) · bioRxiv · doi:10.64898/2026.05.15.725364 · Cited by 1 · see citing works
“…that MCM10 is replaced by the Fork Protection Complex (FPC) ( Sc Tof1-Csm3-Mrc1 / Hs TIM-TIPIN-CLASPIN) and Sc Ctf4, whose binding sites overlap almost all MCM10-CMG attachment points (Baretić, et al. 2020; Jones, et al. 2021; Jenkyn-Bedford et al. 2021; Jones et al. 2023) (Supplementary Fig.”
Self-citationArchaeal and eukaryotic MCM rings sequentially melt DNA for replication initiation
Rasouli, S., Myasnikov, A., & Enemark, E. J. (2026) · Nature Communications · doi:10.1038/s41467-026-70961-8 · Cited by 1 · see citing works
Karri, S., & Yu, C. (2026) · DNA · doi:10.3390/dna6010009 · Cited by 1
“Eukaryotic DNA replication is carried out by a highly conserved molecular machine whose core components are conserved from yeast to humans [12].”
DNA translocation by the CMG helicase: The helical inchworm model
Batra, S., Allwein, B., Wang, Y., Hite, R., & Remus, D. (2026) · Biochemical Society Transactions · doi:10.1042/bst20250145 · Cited by 1 · see citing works
“…lagging strand template from the central channel of the CMG and its specific guidance between the NTDs of Mcm3 and Mcm5 is critical to prevent premature termination via ubiquitylation-mediated CMG unloading [38–40] and to promote efficient initiation of primer synthesis on the lagging strand [37].”
Interpreting the effects of DNA polymerase variants at the structural level
Arnaudi, M., Krzesińska, K., Beltrame, L., Besora, P. S.-I., Tiberti, M., Nilbert, M. C., Rohlin, A., & Papaleo, E. (2026) · Molecular Oncology · doi:10.1002/1878-0261.70255
“In the case of POLE, we used a cryo-EM structure with 2.80 A resolution (PDB ID 7PLO; [24]), in which POLE (chain A) interacts with POLE2 (chain B; POLE 1371-2280 -POLE2 A resolution for the POLE-PCNA complex (PDB ID 9B8T [25]).”
InfluentialParental Histone Recycling During Chromatin Replication
Bi, X. (2025) · Biomolecules · doi:10.3390/biom16010013 · Cited by 1 · see citing works
“That said, the cryo-EM structure is generally in agreement with cryo-EM structures of several reconstituted replication complexes previously reported [58,63–65].”
The non-catalytic DNA polymerase ε subunit is an NPF motif recognition protein
Keskitalo, S., Zámbó, B., Pinar, D. M., Tuhkala, A., Salokas, K., Turunen, T., Deutsch, N., Davey, N., Dosztányi, Z., Varjosalo, M., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-67284-5 · Cited by 1 · see citing works
“Although POLE2 situates on the other end of the replication fork, according to available replisome structures 53,54 , the NPF motifs in all three copies of the trimeric WDHD1 disordered tails are easily within reach of POLE2.”
Lin, J., Zhang, Y.-Z., Zhan, Z.-R., Liang, D., Zhou, X., Zheng, K., Tu, Y.-L., & Yan, S.-J. (2025) · Scientific Reports · doi:10.1038/s41598-025-27559-9 · Cited by 1
“Minichromosome maintenance complex component 5 (MCM5) encodes part of the MCM2–7 helicase, essential for DNA replication 19,20 .”
Metagenomic Applications in the Early Detection of Human Viral Threats
Damian, D. (2025) · Viral Immunology · doi:10.1177/08828245251400169 · Cited by 2 · see citing works
“A 2021 study by Jenkyn-Bedford et al. (2021) used metagenomic datasets combined with phylodynamics to track the evolutionary trajectory of SARS-CoV-2 variants in real time.”
AND-1 is a critical regulator of R-loop dynamics and a target to overcome endocrine resistance
Li, Z.-Q., Peng, Y., Chiang, H.-C., Gao, Y.-J., Chu, C., Zhang, Y., Mughal, M., Liu, C.-Y., Li, R., Pei, H.-D., et al. (2025) · Science Advances · doi:10.1126/sciadv.adv2453 · Cited by 1 · see citing works
“AND-1/ WDHD1 (also known as Ctf4 in yeast) is an acidic nu-cleoplasmic DNA-binding protein that is essential for DNA replication and DNA damage repair ( 24 – 29 ).”
Li, Z., Shinohara, A., Xia, Y.-S., Xu, X.-Z., & Takeda, S. (2026) · Bioessays · doi:10.1002/bies.70185
“To understand how MCM5 UFMylation controls RF speed, we examined published high-resolution cryo-EM structures of the human replisome [163–165].”
Ma, X.-L., Su, B., Ye, A.-X., Wan, R.-Y., Zhao, K.-Y., Zhong, L., Yu, W.-X., Liu, Y.-H., Wu, J.-Y., & Cai, W.-L. (2026) · bioRxiv · doi:10.64898/2026.09.10.750788
FANCJ and RTEL1 facilitate pre-replication complex disassembly following replisome collision.
Cameron, G., Negi, S., Sato, K., Yardimci, S., Kaya, Ç., McClymont, C., Yadav, A. K., Krejčí, J., Knipscheer, P., Polasek-Sedlackova, H., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117860
Li, Y., Wu, D., Shi, Z., Luo, Q., Deng, W., Liu, Q., Lü, A., Chen, W., Qin, G., & Guan, D. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-08365-x
“CDC45, a central component of the CMG helicase complex, facilitates DNA unwinding during replication [85] and promotes G2/M progression, stemness, and EMT in lung adenocarcinoma and hepatocellular carcinoma [86]; in triple-negative breast cancer lines, its knockdown suppresses growth, migration,…”
Mitotic kinase regulation of DNA replication forksPreprint
Shrestha, S., Paukovich, N., Greenfield, S. R., MacFadden, A., Smith, S. N., Bevers, S., & McClure, A. W. (2026) · bioRxiv · doi:10.64898/2026.05.16.725582
“For example, Mrc1 phosphorylation could promote recruitment of the ubiquitin ligase Dia2 to facilitate Mcm7 ubiquitination and subsequent CMG disassembly 48,49 .”
- Authors
- Jenkyn-Bedford, M., Jones, M. L., Baris, Y., Labib, K. P. M., Cannone, G., Yeeles, J. T. P., & Deegan, T. D.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- University of Dundee (GB)
- Corresponding author
- Yeeles, Joseph T. P.
- Deegan, Tom D.
- ORCID
- Venue
- Nature
- Published
- 2021-10-26
- Volume
- 600
- Issue
- 7890
- Pages
- 743-747
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC8695382
- OpenAlex
- W3208795162
- Cited by
- 116
- References
- 33
- Citations by year
- 2026: 17 · 2025: 34 · 2024: 32 · 2023: 26 · 2022: 7
- FWCI
- 5.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo
- Funders
- Wellcome Trust (204678/Z/16/Z)
- UK Research and Innovation (MC_UP_1201/12)
- Cancer Research UK (24558)
- Directorate for Biological Sciences
- Medical Research Council (MC_UU_12016/13, MC_UP_1201/12, MC_UU_12016, MC_UU_00018/4)
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- CMG helicase, E3 ubiquitin ligase, ubiquitination, replication termination, leucine-rich repeat domain, replication fork collapse, eukaryotic DNA replication
- MeSH terms
- DNA, DNA Replication, DNA Helicases, Humans, Cryoelectron Microscopy, Ubiquitin-Protein Ligases, Eukaryota
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