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Risks at the DNA Replication Fork: Effects upon Carcinogenesis and Tumor Heterogeneity
Tony M Mertz1, Victoria Harcy2, Steven A Roberts3
1School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA. mertztony@vetmed.wsu.edu.
Genes
|January 25, 2017
Summary
DNA replication errors in somatic cells drive cancer development. This review examines how replication fork enzyme defects and APOBEC enzymes contribute to mutations, promoting cancer and tumor heterogeneity.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- DNA replication is essential for cell division but errors can cause genetic diseases and cancer.
- Replication errors in tumors lead to mutator phenotypes and heterogeneity, complicating cancer treatment.
- Understanding these errors is crucial for developing effective cancer therapies.
Purpose of the Study:
- To review the role of replication fork enzymes and APOBEC enzymes in DNA mutation and carcinogenesis.
- To highlight how replication stress and metabolic changes influence mutagenic activities at the replication fork.
- To connect DNA replication errors to cancer development and therapeutic challenges.
Main Methods:
- Review of existing tumor data and experimental evidence.
- Analysis of research on replicative polymerases and APOBEC cytidine deaminases.
- Examination of model systems investigating replication stress and metabolic effects.
Main Results:
- Error-prone replicative polymerases promote carcinogenesis.
- APOBEC cytidine deaminases primarily target single-stranded DNA at the replication fork.
- Replication stress and metabolic changes can modulate mutagenic enzyme activity.
Conclusions:
- Defects in replication fork enzymes and dysregulation of DNA-damaging enzymes contribute significantly to cancer.
- Targeting these enzymes and processes may offer new therapeutic strategies for cancer treatment.
- Further research into replication stress and metabolic influences is needed to fully understand carcinogenesis.
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