Background: Despite rising incidence rates of colorectal malignancies, only a few prognostic tools have been implemented in proven clinical routine. Cell division and proliferation play a significant role in malignancies. In terms of colorectal cancer, the impact of proliferation associated proteins is controversially debated. The aim of our study was to examine the expression of topoisomerase II α and minichromosome maintenance protein 6 and to correlate these findings with the clinical data.
Methods: Tissue samples of 619 patients in total were stained using the antibodies Ki-S4 and Ki-MCM6 targeting topoisomerase II α as well as minichromosome maintenance protein 6. The median rate of proliferation was correlated with clinical and follow up data.
Results: The expression rate of minichromosome maintenance protein 6 is significantly higher than the proportion of topoisomerase II α in tumour cells (p < 0.001). A high expression of both proteins coincides with a beneficial outcome for the patient, indicating a favourable prognostic marker (p < 0.001 and p = 0.008).
Conclusions: We have demonstrated that high expression rates of proliferative markers is linked to a beneficial patient outcome. According to the general opinion, a high expression rate correlates with a poor patient outcome. In this study, we were able to refute this assertion.
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http://dx.doi.org/10.1186/s12885-019-5631-3 | DOI Listing |
PLoS Genet
January 2025
Biomedical Science Graduate Program, University of California San Diego, San Diego, California, United States of America.
Proteins with nuclear localization sequences (NLSs) are directed into the cell nucleus through interactions between the NLS and importin proteins. NLSs are generally short motifs rich in basic amino acids; however, identifying NLSs can be challenging due to the lack of a universally conserved sequence. In this study, we characterized the sequence specificity of an essential and conserved NLS in Mcm3, a subunit of the replicative DNA helicase.
View Article and Find Full Text PDFNat Commun
January 2025
Macromolecular Machines Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.
The MCM motor of the eukaryotic replicative helicase is loaded as a double hexamer onto DNA by the Origin Recognition Complex (ORC), Cdc6, and Cdt1. ATP binding supports formation of the ORC-Cdc6-Cdt1-MCM (OCCM) helicase-recruitment complex where ORC-Cdc6 and one MCM hexamer form two juxtaposed rings around duplex DNA. ATP hydrolysis by MCM completes MCM loading but the mechanism is unknown.
View Article and Find Full Text PDFCells
December 2024
Karmanos Cancer Institute, Department of Oncology, School of Medicine, Wayne State University, 4100 John R Street, Detroit, MI 48201, USA.
The DNA replication machinery is highly conserved from bacteria to eukaryotic cells. Faithful DNA replication is vital for cells to transmit accurate genetic information to the next generation. However, both internal and external DNA damages threaten the intricate DNA replication process, leading to the activation of the DNA damage response (DDR) system.
View Article and Find Full Text PDFAsian J Androl
January 2025
Department of Andrology, The Center for Men's Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200000, China.
Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 (MCMDC2) genes in 768 NOA patients by whole-exome sequencing (WES).
View Article and Find Full Text PDFNat Commun
January 2025
DNA Replication Group, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK.
Human DNA licensing initiates replication fork assembly and DNA replication. This reaction promotes the loading of the hMCM2-7 complex on DNA, which represents the core of the replicative helicase that unwinds DNA during S-phase. Here, we report the reconstitution of human DNA licensing using purified proteins.
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