4.7 Article

Cdt1 overexpression drives colorectal carcinogenesis through origin overlicensing and DNA damage

Related references

Note: Only part of the references are listed.
Article Pharmacology & Pharmacy

Small Molecule Inhibitor Targeting CDT1/Geminin Protein Complex Promotes DNA Damage and Cell Death in Cancer Cells

Nikolaos Karantzelis et al.

Summary: DNA replication initiation requires the loading of MCM2-7 complexes at the origins of replication during G1. Replication licensing is crucial for chromatin to be competent for DNA replication and its regulation is important for preventing abnormal DNA replication and genomic instability. CDT1 is a critical factor in replication licensing and it is controlled by redundant mechanisms involving Geminin, an inhibitor of CDT1. Abnormal expression of CDT1 and Geminin has been linked to tumorigenesis in vivo and is observed in various human tumors. This study developed an in vitro assay for screening small-molecule inhibitors targeting the CDT1/Geminin protein complex. The most potent compound, AF615, was found to specifically inhibit Geminin binding to CDT1 both in vitro and in cells. AF615 also induced DNA damage, inhibited DNA synthesis, and selectively reduced viability in cancer cell lines, and this effect was dependent on CDT1. The findings suggest that AF615 could be a useful tool for studying the role of the CDT1/Geminin protein complex in replication licensing and origin firing.

FRONTIERS IN PHARMACOLOGY (2022)

Article Multidisciplinary Sciences

Signatures of copy number alterations in human cancer

Christopher D. Steele et al.

Summary: Gains and losses of DNA are prevalent in cancer and contribute to cancer initiation, progression, and therapeutic resistance. A study identified 21 copy number signatures that explain 97% of the sample's copy number patterns.

NATURE (2022)

Article Medicine, General & Internal

PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer

Andrea Cercek et al.

Summary: This study found that mismatch repair-deficient, locally advanced rectal cancer is highly sensitive to PD-1 blockade. Additionally, no adverse events of grade 3 or higher have been reported, and no cases of progression or recurrence have been observed. Longer follow-up is needed to assess the duration of response.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

Article Biochemistry & Molecular Biology

TNMplot.com: A Web Tool for the Comparison of Gene Expression in Normal, Tumor and Metastatic Tissues

Aron Bartha et al.

Summary: This study established an integrated database of gene expression data from tumor and metastatic tissues, identifying potential therapeutic targets for different cancer types. The online platform allows real-time mining and analysis of the database, providing valuable insights for cancer research and treatment.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Biology

Twelve years of SAMtools and BCFtools

Petr Danecek et al.

Summary: SAMtools and BCFtools are widely used tools for processing high-throughput sequencing data, with a history of 12 years of continuous development and improvement. These packages have been utilized in various software projects and genomic pipelines and are freely available on GitHub.

GIGASCIENCE (2021)

Article Biochemistry & Molecular Biology

Spatially organized multicellular immune hubs in human colorectal cancer

Karin Pelka et al.

Summary: By analyzing the transcriptional profiles of cells in tumors, differences in immune responses between mismatch repair-deficient (MMRd) and mismatch repair-proficient (MMRp) tumors were identified, as well as the logic behind the interaction of malignant and immune cells discovered within tumors.
Article Multidisciplinary Sciences

Dynamics of replication origin over-activation

Haiqing Fu et al.

Summary: Safeguards against excess DNA replication are often dysregulated in cancer cells, leading researchers to investigate the DNA synthesis patterns in cancer cells undergoing partial genome re-replication. The study reveals that re-replication in cancer cells results in aberrant replication fork dynamics and a skewed distribution of replication initiation, causing over-duplication in early-replicating genomic regions.

NATURE COMMUNICATIONS (2021)

Article Multidisciplinary Sciences

The repertoire of mutational signatures in human cancer

Ludmil B. Alexandrov et al.

NATURE (2020)

Article Genetics & Heredity

DNA Rereplication Is Susceptible to Nucleotide-Level Mutagenesis

Duyen T. Bui et al.

GENETICS (2019)

Article Biochemistry & Molecular Biology

GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis

Zefang Tang et al.

NUCLEIC ACIDS RESEARCH (2019)

Review Biochemistry & Molecular Biology

Replication Licensing Aberrations, Replication Stress, and Genomic Instability

Michalis Petropoulos et al.

TRENDS IN BIOCHEMICAL SCIENCES (2019)

Article Cell Biology

Lgr5+ intestinal stem cells reside in an unlicensed G1 phase

Thomas D. Carroll et al.

JOURNAL OF CELL BIOLOGY (2018)

Article Oncology

Geminin ablation in vivo enhances tumorigenesis through increased genomic instability

Spyridon Champeris Tsaniras et al.

JOURNAL OF PATHOLOGY (2018)

Article Gastroenterology & Hepatology

Microbiota modification by probiotic supplementation reduces colitis associated colon cancer in mice

Maria Carolina S. Mendes et al.

WORLD JOURNAL OF GASTROENTEROLOGY (2018)

Article Multidisciplinary Sciences

High-resolution TADs reveal DNA sequences underlying genome organization in flies

Fidel Ramirez et al.

NATURE COMMUNICATIONS (2018)

Article Multidisciplinary Sciences

Intragenic origins due to short G1 phases underlie oncogene-induced DNA replication stress

Morgane Macheret et al.

NATURE (2018)

Article Cell Biology

Geminin is an indispensable inhibitor of Cdt1 in mouse embryonic stem cells

Masaki Hosogane et al.

GENES TO CELLS (2017)

Article Multidisciplinary Sciences

The prognostic significance of Cdc6 and Cdt1 in breast cancer

Ravikiran Mahadevappa et al.

SCIENTIFIC REPORTS (2017)

Article Cell Biology

In Vivo DNA Re-replication Elicits Lethal Tissue Dysplasias

Sergio Munoz et al.

CELL REPORTS (2017)

Article Biochemistry & Molecular Biology

deepTools2: a next generation web server for deep-sequencing data analysis

Fidel Ramirez et al.

NUCLEIC ACIDS RESEARCH (2016)

Article Biochemistry & Molecular Biology

ATR-Mediated Phosphorylation of FANCI Regulates Dormant Origin Firing in Response to Replication Stress

Yu-Hung Chen et al.

MOLECULAR CELL (2015)

Article Multidisciplinary Sciences

WWOX, the common fragile site FRA16D gene product, regulates ATM activation and the DNA damage response

Mohammad Abu-Odeh et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2014)

Article Biochemistry & Molecular Biology

The Landscape of Microsatellite Instability in Colorectal and Endometrial Cancer Genomes

Tae-Min Kim et al.

Article Biochemistry & Molecular Biology

Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal

Jianjiong Gao et al.

SCIENCE SIGNALING (2013)

Article Immunology

Differential Geminin Requirement for Proliferation of Thymocytes and Mature T Cells

Dimitris Karamitros et al.

JOURNAL OF IMMUNOLOGY (2010)

Review Cell Biology

Genomic instability - an evolving hallmark of cancer

Simona Negrini et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2010)

Article Biochemical Research Methods

Fast and accurate short read alignment with Burrows-Wheeler transform

Heng Li et al.

BIOINFORMATICS (2009)

Article Oncology

Selective Killing of Cancer Cells by Suppression of Geminin Activity

Wenge Zhu et al.

CANCER RESEARCH (2009)

Article Biochemical Research Methods

Buccal micronucleus cytome assay

Philip Thomas et al.

NATURE PROTOCOLS (2009)

Article Oncology

Deregulated overexpression of hCdtl and hCdc6 promotes malignant Behavior

Michalis Liontos et al.

CANCER RESEARCH (2007)

Article Multidisciplinary Sciences

Identification of stem cells in small intestine and colon by marker gene Lgr5

Nick Barker et al.

NATURE (2007)

Article Biochemistry & Molecular Biology

Cdt1 transgenic mice develop lymphoblastic lymphoma in the absence of p53

J Seo et al.

ONCOGENE (2005)

Article Biochemistry & Molecular Biology

A p53-dependent checkpoint pathway prevents rereplication

C Vaziri et al.

MOLECULAR CELL (2003)