Genes, Vol. 12, Pages 1146: DNA Polymerase θ: A Cancer Drug Target with Reverse Transcriptase Activity
Genes, Vol. 12, Pages 1146: DNA Polymerase θ: A Cancer Drug Target with Reverse Transcriptase Activity
Genes doi: 10.3390/genes12081146
Authors:
Xiaojiang S. Chen
Richard T. Pomerantz
The emergence of precision medicine from the development of Poly (ADP-ribose) polymerase (PARP) inhibitors that preferentially kill cells defective in homologous recombination has sparked wide interest in identifying and characterizing additional DNA repair enzymes that are synthetic lethal with HR factors. DNA polymerase theta (Polθ) is a validated anti-cancer drug target that is synthetic lethal with HR factors and other DNA repair proteins and confers cellular resistance to various genotoxic cancer therapies. Since its initial characterization as a helicase-polymerase fusion protein in 2003, many exciting and unexpected activities of Polθ in microhomology-mediated end-joining (MMEJ) and translesion synthesis (TLS) have been discovered. Here, we provide a short review of Polθ‘s DNA repair activities and its potential as a drug target and highlight a recent report that reveals Polθ as a naturally occurring reverse transcriptase (RT) in mammalian cells.
Source: Genes - Category: Genetics & Stem Cells Authors: Xiaojiang S. Chen Richard T. Pomerantz Tags: Review Source Type: research