Cancer is associated with genomic instability and aging. Genomic instability stimulates tumorigenesis, whereas deregulation of oncogenes accelerates DNA replication and increases genomic instability. It is therefore reasonable to assume a positive feedback loop between genomic instability and oncogenic stress. Consistent with this premise, overexpression of the MYC transcription factor increases the phosphorylation of serine 139 in histone H2AX (member X of the core histone H2A family), which forms so-called γH2AX, the most widely recognized surrogate biomarker of double-stranded DNA breaks (DSBs). Paradoxically, oncogenic MYC can also promote the resistance of cancer cells to chemotherapeutic DNA-damaging agents such as cisplatin, clearly implying an antagonistic role of MYC in genomic instability. In this review, we summarize the underlying mechanisms of the conflicting functions of MYC in genomic instability and discuss when and how the oncoprotein exerts the contradictory roles in induction of DSBs and protection of cancer-cell genomes.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485522 | PMC |
| http://dx.doi.org/10.3390/genes8060158 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Michigan Medical School, Ann Arbor, MI, USA.
Background: The transfer of mitochondrial DNA into the nuclear genomes of eukaryotes (Numts) has been linked to lifespan in non-human species and recently demonstrated to occur in rare instances from one human generation to the next.
Method: Here we investigated numtogenesis dynamics in humans in two ways. First, we quantified Numts in 1,187 post-mortem brain and blood samples from different individuals.
IDO1 inhibitor enhances the effectiveness of PD-1 blockade in microsatellite stable colorectal cancer by promoting macrophage pro-inflammatory phenotype polarization.
Cancer Immunol Immunother
January 2025
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
Microsatellite stable (MSS) colorectal cancer (CRC) is a subtype of CRC that generally exhibits resistance to immunotherapy, particularly immune checkpoint inhibitors such as PD-1 blockade. This study investigates the effects and underlying mechanisms of combining PD-1 blockade with IDO1 inhibition in MSS CRC. Bioinformatics analyses of TCGA-COAD and TCGA-READ cohorts revealed significantly elevated IDO1 expression in CRC tumors, correlating with tumor mutation burden across TCGA datasets.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Background: Studies of the genetics of Alzheimer's disease (AD) have largely focused on single nucleotide variants and short insertions/deletions. However, much of the disease heritability has yet to be uncovered, suggesting that other forms of genetic variation promote substantial portions of genetic risk. Uncovering the genetic basis of AD can lead to new disease biomarkers and delineate disease mechanisms.
View Article and Find Full Text PDFClinicopathological features of Lynch syndrome pedigrees with MSH2 c.351G>A gene variant.
Mol Genet Genomic Med
January 2025
Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, Liaoning, China.
Background: Lynch syndrome (LS) is an autosomal-dominant disorder that increases the risk of many cancers. To identify novel or rare pathogenic variants of MMR genes associated with LS, especially in Chinese pedigrees.
Methods: One four-generation Chinese Han family from northeast China with 29 members was enrolled.
Modern biology of extrachromosomal DNA: A decade-long voyage of discovery.
Cell Res
January 2025
Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Genomic instability is a hallmark of cancer and is a major driving force of tumorigenesis. A key manifestation of genomic instability is the formation of extrachromosomal DNAs (ecDNAs) - acentric, circular DNA molecules ranging from 50 kb to 5 Mb in size, distinct from chromosomes. Ontological studies have revealed that ecDNA serves as a carrier of oncogenes, immunoregulatory genes, and enhancers, capable of driving elevated transcription of its cargo genes and cancer heterogeneity, leading to rapid tumor evolution and therapy resistance.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!