ArticleThe Journal of biological chemistry2011
The Cdc45·Mcm2-7·GINS protein complex in trypanosomes regulates DNA replication and interacts with two Orc1-like proteins in the origin recognition complex.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 61 citations in OpenAlex.
- Stage-specific MCM protein expression inFrontiers in cellular and infection microbiology · 2025Article
- Unwinding Helicase MCM Functionality for Diagnosis and Therapeutics of Replication Abnormalities Associated with Cancer: A Review.Molecular diagnosis & therapy · 2024Review
- Article
- High abundance of CDC45 inhibits cell proliferation through elevation of HSPA6.Cell proliferation · 2022Article
- The CRK2-CYC13 complex functions as an S-phase cyclin-dependent kinase to promote DNA replication in Trypanosoma brucei.BMC biology · 2021Article
- DNA replication protein Cdc45 directly interacts with PCNA via its PIP box in Leishmania donovani and the Cdc45 PIP box is essential for cell survival.PLoS pathogens · 2020Article
- Evolution of metabolic capabilities and molecular features of diplonemids, kinetoplastids, and euglenids.BMC biology · 2020Article
- Transcriptional and genomic parallels between the monoxenous parasite Herpetomonas muscarum and Leishmania.PLoS genetics · 2019Article
- Genome-wide function of MCM-BP in Trypanosoma brucei DNA replication and transcription.Nucleic acids research · 2019Article
- The novel GINS4 axis promotes gastric cancer growth and progression by activating Rac1 and CDC42.Theranostics · 2019Article
- Conservation and Variation in Strategies for DNA Replication of Kinetoplastid Nuclear Genomes.Current genomics · 2018Review
- Nuclear DNA Replication in Trypanosomatids: There Are No Easy Methods for Solving Difficult Problems.Trends in parasitology · 2017Review
- MCM2-regulated functional networks in lung cancer by multi-dimensional proteomic approach.Scientific reports · 2017Article
- Genome-wide and protein kinase-focused RNAi screens reveal conserved and novel damage response pathways in Trypanosoma brucei.PLoS pathogens · 2017Article
- The Protein Neddylation Pathway in Trypanosoma brucei: FUNCTIONAL CHARACTERIZATION AND SUBSTRATE IDENTIFICATION.The Journal of biological chemistry · 2017Article
- Diverged composition and regulation of the Trypanosoma brucei origin recognition complex that mediates DNA replication initiation.Nucleic acids research · 2016Article
- Single molecule analysis of Trypanosoma brucei DNA replication dynamics.Nucleic acids research · 2015Article
- Deviating the level of proliferating cell nuclear antigen in Trypanosoma brucei elicits distinct mechanisms for inhibiting proliferation and cell cycle progression.Cell cycle (Georgetown, Tex.) · 2015Article
- Centrin3 in trypanosomes maintains the stability of a flagellar inner-arm dynein for cell motility.Nature communications · 2014Article
- The Aurora B kinase in Trypanosoma brucei undergoes post-translational modifications and is targeted to various subcellular locations through binding to TbCPC1.Molecular microbiology · 2014Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Accurate DNA replication requires a complex interplay of many regulatory proteins at replication origins. The CMG (Cdc45·Mcm2-7·GINS) complex, which is composed of Cdc45, Mcm2-7, and the GINS (Go-Ichi-Ni-San) complex consisting of Sld5 and Psf1 to Psf3, is recruited by Cdc6 and Cdt1 onto origins bound by the heterohexameric origin recognition complex (ORC) and functions as a replicative helicase. Trypanosoma brucei, an early branched microbial eukaryote, appears to express an archaea-like ORC consisting of a single Orc1/Cdc6-like protein. However, unlike archaea, trypanosomes possess components of the eukaryote-like CMG complex, but whether they form an active helicase complex, associate with the ORC, and regulate DNA replication remains unknown. Here, we demonstrated that the CMG complex is formed in vivo in trypanosomes and that Mcm2-7 helicase activity is activated by the association with Cdc45 and the GINS complex in vitro. Mcm2-7 and GINS proteins are confined to the nucleus throughout the cell cycle, whereas Cdc45 is exported out of the nucleus after DNA replication, indicating that nuclear exclusion of Cdc45 constitutes one mechanism for preventing DNA re-replication in trypanosomes. With the exception of Mcm4, Mcm6, and Psf1, knockdown of individual CMG genes inhibits DNA replication and cell proliferation. Finally, we identified a novel Orc1-like protein, Orc1b, as an additional component of the ORC and showed that both Orc1b and Orc1/Cdc6 associate with Mcm2-7 via interactions with Mcm3. All together, we identified the Cdc45·Mcm2-7·GINS complex as the replicative helicase that interacts with two Orc1-like proteins in the unusual origin recognition complex in trypanosomes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.