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2023 3
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Mechanisms for licensing origins of DNA replication in eukaryotic cells.
Stillman B, Diffley JFX, Iwasa JH. Stillman B, et al. Nat Struct Mol Biol. 2025 Jul;32(7):1143-1153. doi: 10.1038/s41594-025-01587-5. Epub 2025 Jun 30. Nat Struct Mol Biol. 2025. PMID: 40588663 Review.
In this Review, we discuss and contextualize recent findings identifying the mechanisms of origin recognition and pre-RC assembly mediated by the origin recognition complex (ORC), Cdc6 and the Mcm2-Mcm7 (Mcm2-7) hexamer bound to Cdt1. We also present comprehensive videos t …
In this Review, we discuss and contextualize recent findings identifying the mechanisms of origin recognition and pre-RC assembly mediated b …
Two coral fluorescent proteins of distinct colors for sharp visualization of cell-cycle progression.
Ando R, Sakaue-Sawano A, Shoda K, Miyawaki A. Ando R, et al. Cell Struct Funct. 2023 Jul 29;48(2):135-144. doi: 10.1247/csf.23028. Epub 2023 Jul 30. Cell Struct Funct. 2023. PMID: 37394513 Free PMC article.
We fused h2-3 and AzaleaB5 to the ubiquitination domains of human Geminin and Cdt1, respectively, to generate a new color variant of Fucci (Fluorescent Ubiquitination-based Cell-Cycle Indicator): Fucci5. ...
We fused h2-3 and AzaleaB5 to the ubiquitination domains of human Geminin and Cdt1, respectively, to generate a new color variant of …
MCM double hexamer loading visualized with human proteins.
Weissmann F, Greiwe JF, Pühringer T, Eastwood EL, Couves EC, Miller TCR, Diffley JFX, Costa A. Weissmann F, et al. Nature. 2024 Dec;636(8042):499-508. doi: 10.1038/s41586-024-08263-6. Epub 2024 Nov 27. Nature. 2024. PMID: 39604733 Free PMC article.
Our current understanding of how the double hexamer is assembled by the origin recognition complex (ORC), CDC6 and CDT1 comes mostly from budding yeast. Here we characterize human double hexamer (hDH) loading using biochemical reconstitution and cryo-electron microscopy wi …
Our current understanding of how the double hexamer is assembled by the origin recognition complex (ORC), CDC6 and CDT1 comes mostly …
Geminin inhibits DNA replication licensing by sterically blocking CDT1-MCM2 interactions.
Tomkins J, Edwardes LV, Faull SV, Peach M, Gillespie PJ, Leber V, Schmidt A, Bounoua H, Sim N, Camarillo R, Blow JJ, Barr AR, Barnard A, Speck C. Tomkins J, et al. Nat Commun. 2025 Dec 9;16(1):11040. doi: 10.1038/s41467-025-67073-0. Nat Commun. 2025. PMID: 41365879 Free PMC article.
AlphaFold modelling provides structural insights into an N-terminal CDT1-binding helix of geminin, which proves essential for inhibition. Structural docking of the CDT1-geminin complex into the ORC-CDC6-CDT1-MCM2-7 (OCCM) assembly shows that geminin's long co …
AlphaFold modelling provides structural insights into an N-terminal CDT1-binding helix of geminin, which proves essential for inhibit …
BRCA2 reversion mutation-independent resistance to PARP inhibition through impaired DNA prereplication complex function.
Pappas K, Ferrari M, Smith P, Nandakumar S, Khan Z, Young SB, LaClair J, Russo MV, Huang-Hobbs E, Schultz N, Abida W, Karthaus W, Jasin M, L Sawyers C. Pappas K, et al. Proc Natl Acad Sci U S A. 2025 Jun 10;122(23):e2426743122. doi: 10.1073/pnas.2426743122. Epub 2025 Jun 3. Proc Natl Acad Sci U S A. 2025. PMID: 40460119 Free PMC article.
Moreover, sensitivity to PARP inhibition was restored in Brca2(delta/delta), Cdc6-depleted prostate cells by knockdown of geminin, a negative regulator of Cdt1, further implicating the critical role of a functional pre-RC complex in PARPi sensitivity. ...Of note, a pharmac …
Moreover, sensitivity to PARP inhibition was restored in Brca2(delta/delta), Cdc6-depleted prostate cells by knockdown of geminin, a negativ …
Temporal control of human DNA replication licensing by CDK4/6-RB signalling and chemical genetics.
Sosenko Piscitello A, Nilsson AS, Hawgood M, Sayyid AH, Dionellis VS, Giglio G, Urién B, Bajgain P, Ntallis SG, Bartek J, Halazonetis TD, Lemmens B. Sosenko Piscitello A, et al. Nat Commun. 2025 Sep 12;16(1):8268. doi: 10.1038/s41467-025-63669-8. Nat Commun. 2025. PMID: 40940326 Free PMC article.
The first step in replication is origin licensing, when minichromosome maintenance (MCM) helicases are loaded onto DNA by CDC6, CDT1 and the origin recognition complex (ORC). In yeast, origin licensing starts when CDK activity plummets in G1 phase, reinforcing the view tha …
The first step in replication is origin licensing, when minichromosome maintenance (MCM) helicases are loaded onto DNA by CDC6, CDT1 …
Histone Deacetylase Inhibitors Target DNA Replication Regulators and Replication Stress in Ewing Sarcoma Cells.
Koppenhafer SL, Geary EL, Thomas MV, Croushore EE, Zimmerman JAO, Gedminas JM, Quelle DE, Dodd RD, Gordon DJ. Koppenhafer SL, et al. Cancer Res Commun. 2025 Jun 1;5(6):1034-1048. doi: 10.1158/2767-9764.CRC-25-0058. Cancer Res Commun. 2025. PMID: 40478628 Free PMC article.
Moreover, transcriptome analyses identified that HDAC inhibitors downregulate the expression of multiple components of the prereplication complex, including the minichromosome maintenance complex 2-7 (MCM2-7) proteins and CDT1, that are essential for genomic DNA replicatio …
Moreover, transcriptome analyses identified that HDAC inhibitors downregulate the expression of multiple components of the prereplication co …
Genotype-phenotype associations in microtia: a systematic review.
Wahdini SI, Idamatussilmi F, Pramanasari R, Prawoto AN, Wungu CDK, Putri IL, Gunadi. Wahdini SI, et al. Orphanet J Rare Dis. 2024 Apr 9;19(1):152. doi: 10.1186/s13023-024-03142-9. Orphanet J Rare Dis. 2024. PMID: 38594752 Free PMC article.
In the syndromic microtia group, the most common genes were TCOF1 (43.75%), SIX2 (4.69%), and HSPA9 (4.69%), while in the non-syndromic microtia group, the most frequently found gene was GSC exon 2 (25%), FANCB (16.67%), HOXA2 (8.33%), GSC exon 3 (8.33%), MARS1 (8.33%), and CD …
In the syndromic microtia group, the most common genes were TCOF1 (43.75%), SIX2 (4.69%), and HSPA9 (4.69%), while in the non-syndromic micr …
GMNN mutations cause female infertility characterized by preimplantation embryo arrest through regulating DNA re-replication.
Zhang H, Su W, Jiang X, Wang Y, Yang B, Wan X, Li C, Zhao S, Zhang C, Zhao S, Bian Y, Li M, Wu K, Gong F, Lin G, Zheng W, Zhao H, Chen ZJ. Zhang H, et al. Sci China Life Sci. 2025 Aug;68(8):2420-2430. doi: 10.1007/s11427-024-2837-9. Epub 2025 May 29. Sci China Life Sci. 2025. PMID: 40455380
Geminin, encoded by the GMNN gene, plays an important role in preventing DNA re-replication by inhibiting CDT1. Here, using whole-exome sequencing and Sanger sequencing, we identified three rare missense mutations of GMNN in females with preimplantation arrest, following a …
Geminin, encoded by the GMNN gene, plays an important role in preventing DNA re-replication by inhibiting CDT1. Here, using whole-exo …
SETD3-mediated histidine methylation of MCM7 regulates DNA replication by facilitating chromatin loading of MCM.
Duan H, Wang S, Shu WJ, Tong Y, Long HZ, Li G, Du HN, Zhao MJ. Duan H, et al. Sci China Life Sci. 2025 Mar;68(3):793-808. doi: 10.1007/s11427-023-2600-0. Epub 2024 Oct 24. Sci China Life Sci. 2025. PMID: 39455502
Biochemical studies reveal that SETD3 binds MCM mainly during S phase, which is required for the CDT1-mediated chromatin loading of MCM. This MCM loading relies on histidine-459 methylation (H459me) on MCM7 which is catalyzed by SETD3. ...
Biochemical studies reveal that SETD3 binds MCM mainly during S phase, which is required for the CDT1-mediated chromatin loading of M …
42 results