Risks at the DNA Replication Fork: Effects upon Carcinogenesis and Tumor Heterogeneity
AbstractThe ability of all organisms to copy their genetic information via DNA replication is a prerequisite for cell division and a biological imperative of life. In multicellular organisms, however, mutations arising from DNA replication errors in the germline and somatic cells are the basis of genetic diseases and cancer, respectively. Within human tumors, replication errors additionally contribute to mutator phenotypes and tumor heterogeneity, which are major confounding factors for cancer therapeutics. Successful DNA replication involves the coordination of many large-scale, complex cellular processes. In this review, we focus on the roles that defects in enzymes that normally act at the replication fork and dysregulation of enzymes that inappropriately damage single-stranded DNA at the fork play in causing mutations that contribute to carcinogenesis. We focus on tumor data and experimental evidence that error-prone variants of replicative polymerases promote carcinogenesis and on research indicating that the primary target mutated by APOBEC (apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like) cytidine deaminases is ssDNA present at the replication fork. Furthermore, we discuss evidence from model systems that indicate replication stress and other cancer-associated metabolic changes may modulate mutagenic enzymatic activities at the replication fork. View Full-Text
Scifeed alert for new publicationsNever miss any articles matching your research from any publisher
- Get alerts for new papers matching your research
- Find out the new papers from selected authors
- Updated daily for 49'000+ journals and 6000+ publishers
- Define your Scifeed now
Mertz, T.M.; Harcy, V.; Roberts, S.A. Risks at the DNA Replication Fork: Effects upon Carcinogenesis and Tumor Heterogeneity. Genes 2017, 8, 46.
Mertz TM, Harcy V, Roberts SA. Risks at the DNA Replication Fork: Effects upon Carcinogenesis and Tumor Heterogeneity. Genes. 2017; 8(1):46.Chicago/Turabian Style
Mertz, Tony M.; Harcy, Victoria; Roberts, Steven A. 2017. "Risks at the DNA Replication Fork: Effects upon Carcinogenesis and Tumor Heterogeneity." Genes 8, no. 1: 46.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.