Ask about this productRelated genes to: CDC45L antibody
- Gene:
- CDC45 NIH gene
- Name:
- cell division cycle 45
- Previous symbol:
- CDC45L2, CDC45L
- Synonyms:
- -
- Chromosome:
- 22q11.21
- Locus Type:
- gene with protein product
- Date approved:
- 1998-09-08
- Date modifiied:
- 2014-11-19
Related products to: CDC45L antibody
Related articles to: CDC45L antibody
- Regulated helicase activation by DDK kinase is central for genome stability. However, how DDK phosphorylation primes the MCM2-7 double hexamer (DH) for Sld3-Sld7 binding and Cdc45 loading remained unclear. We define this mechanism through cryo-EM structures of MCM2-7 DH-Sld3-Sld7 (MS) and MCM2-7 DH-Sld3-Sld7-Cdc45 (MSC). We reveal that the autoinhibitory Mcm4 tail engages not only Mcm4 but also Mcm6. Upon DDK-dependent phosphorylation, both of these sites become accessible. In the context of the MS structure, we identify that two short Sld3 motifs that contact Mcm4 and Mcm6 read out the DH phosphorylation state, while the Sld3 Treslin domain (STD) binds to Mcm2. In the MSC structure, Cdc45 dislodges the Sld3 STD from Mcm2, allowing Sld3 to position Cdc45 at the Mcm2/Mcm5 interface. Mutagenesis of the Sld3 STD-Cdc45 interface disrupts Cdc45 loading, validating this interaction. Together, our data reveal a phosphorylation-encoded mechanism coupling DDK-activated Mcm4/Mcm6 surfaces to distal Cdc45 placement, explaining how firing factors choreograph the DH-to-CMG transition. - Source: PubMed
Publication date: 2026/08/14
Noguchi YasunoriSaleh AlmutasemSchneider SarahIvanova Marina EChen Zhuo AngelRanjha LepakshiAramayo RicardoTognetti SilviaFaull Sarah VRappsilber JuriSpeck Christian - Meier-Gorlin syndrome 7 (MGORS7) is a rare autosomal recessive disorder characterized by primordial dwarfism, craniosynostosis, and patellar aplasia, caused by pathogenic variants of . Here, we report a Chinese patient presenting with classic hallmarks of MGORS7 alongside atypical clinical features, including hearing and visual impairments. - Source: PubMed
Publication date: 2026/08/24
Zhao YingFu YiyangZhang ShuyingHan YuxinZhu JinhuiLiu WanqiLi ShuxianXiao DanLiu YuanWang LinZhang RuixueCheng WenjingRen KaitaoZhang XiaoruiChen MingyueAbdullah Kalsoom Umm-E-Bibi NousheenKhan SaadullahFan FengniJia TingLin XiangdongLi WeiLi ZhaoNishimura GenYamada TakahiroCai NaShukunami ChisaTian ZhiqiangChen XiaoxuIkegawa ShiroQiang RongGuo Long - During eukaryotic DNA replication initiation, inactive MCM2-7 double-hexamers assembled at replication origins must be converted into two active CMG helicases, yet how this transition is coupled to origin DNA unwinding in vivo remains unclear. Here, we identify a DNA-bound intermediate with an extended genomic footprint that forms during helicase activation. Genome-wide mapping of initial strand separation reveals that DNA unwinding initiates near the N-terminal interface of opposing MCM2-7 hexamers. At these sites, the origin DNA exhibits a conserved AT-rich/GC-rich/AT-rich sequence architecture centred under the helicase complex, which is associated with an elevated DNA melting probability. We further show that restricting hexamer splitting delays release of the Cdc45-loading factor Sld3, demonstrating that mechanical transitions during helicase activation are tightly coupled to complex disassembly. Finally, we provide in vivo evidence that single-stranded DNA is ejected through a specialised DNA exit gate at the Mcm2/5 interface during helicase activation, which is dispensable for ongoing DNA synthesis. Together, these findings establish a mechanistic framework for how replication origins are remodelled to initiate DNA replication and reveal key intermediates and DNA transactions during helicase activation. - Source: PubMed
Publication date: 2026/07/23
Weekes ChristopherWillerding LiaKhadayate Sanjay PLiebl KorbinianMossler AudreyMontoya AlexRauthe VanessaKarimi Mohammad MZacharias MartinUlrich Helle DSpeck ChristianReuter L Maximilian - Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, with limited therapeutic efficacy due to tumor heterogeneity in conventional treatments. In the present study, an integrative, network pharmacology approach was employed to elucidate the multi-target mechanism of action of phytochemicals derived from Glossocardia bosvallia against NSCLC. Among 38 phytocompounds identified, 31 compounds that satisfied pharmacokinetic properties were selected for subsequent analysis. Ligand-based target prediction identified 429 potential protein targets, which are integrated with the top 250 differentially expressed genes obtained from the GSE33532 dataset. Intersection analysis identified eight therapeutic targets: PTGES, SRD5A1, CDK1, KIF11, TOP2A, CDC45, MB, and CHEK1. Protein-protein interaction and enrichment analyses demonstrated that these targets are predominantly involved in cell cycle regulation, mitotic cell cycle, and DNA replication pathways. Gene expression analysis demonstrated significant overexpression of the prioritized targets in NSCLC tissues, while survival analysis identified CHEK1 as the gene significantly associated with survival (p < 0.05). Molecular docking identified TOP2A_quinic acid as the most favorable complex, exhibiting a binding affinity of -12.27 kcal/mol, KIF11_linoleic acid as -12.10 kcal/mol and CHEK1_2,3-dihydro-3,5-dihydroxy-6-methyl-4h-pyran-4-one as -6.75 kcal/mol, which was further validated by dynamic simulations, principal component analysis based free energy landscape, and DSSP analysis, confirming the stability of the protein. This integrative framework provides a robust strategy for identifying biologically relevant and therapeutically actionable targets supporting the potential of G. bosvallia-derived phytochemicals as promising candidates for NSCLC. - Source: PubMed
Publication date: 2026/08/04
Kulandhaivel Soundar RajanStalin AntonyMuthuramalingam PandiyanSivaprakasam BalasubramanianJesudass Joseph Sahayarayan - Cervical cancer remains a major global health challenge, particularly in low-resource settings where treatment efficacy is limited by drug resistance and toxicity. Although (Sanqi) has demonstrated anticancer activity, its molecular mechanisms against cervical cancer remain insufficiently understood. - Source: PubMed
Publication date: 2026/07/10
Kamal ShahQin ChenWang YanjuanHe RuilinAmjad Kamal MohammadLi Wenji