Simultaneous disruption of two DNA polymerases, Polη and Polζ, in Avian DT40 cells unmasks the role of Polη in cellular response to various DNA lesions. | LitMetric
CREST Research Project, Japan Science and Technology, Radiation Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Published: October 2010
AI Article Synopsis
Article Abstract
Replicative DNA polymerases are frequently stalled by DNA lesions. The resulting replication blockage is released by homologous recombination (HR) and translesion DNA synthesis (TLS). TLS employs specialized TLS polymerases to bypass DNA lesions. We provide striking in vivo evidence of the cooperation between DNA polymerase η, which is mutated in the variant form of the cancer predisposition disorder xeroderma pigmentosum (XP-V), and DNA polymerase ζ by generating POLη(-/-)/POLζ(-/-) cells from the chicken DT40 cell line. POLζ(-/-) cells are hypersensitive to a very wide range of DNA damaging agents, whereas XP-V cells exhibit moderate sensitivity to ultraviolet light (UV) only in the presence of caffeine treatment and exhibit no significant sensitivity to any other damaging agents. It is therefore widely believed that Polη plays a very specific role in cellular tolerance to UV-induced DNA damage. The evidence we present challenges this assumption. The phenotypic analysis of POLη(-/-)/POLζ(-/-) cells shows that, unexpectedly, the loss of Polη significantly rescued all mutant phenotypes of POLζ(-/-) cells and results in the restoration of the DNA damage tolerance by a backup pathway including HR. Taken together, Polη contributes to a much wide range of TLS events than had been predicted by the phenotype of XP-V cells.
Streptozotocin (STZ) is widely used as a pancreatic beta-cell toxin to induce experimental diabetes in rodents. Strain-dependent variations in STZ-induced diabetes susceptibility have been reported in mice. Differences in STZ-induced diabetes susceptibility are putatively related to pancreatic beta-cell fragility via DNA damage response.
University of Technology Sydney, Sydney, Australia; Institute for Biomedical Materials and Devices, University of Technology Sydney, Sydney, Australia. Electronic address:
Research Question: Can a biomimetic microfluidic sperm sorter isolate motile sperm while minimizing DNA damage in comparison with density gradient centrifugation (DGC)?
Design: This was a two-phase study of 61 men, consisting of a proof-of-concept study with 21 donated semen samples in a university research laboratory, followed by a diagnostic andrology study with 40 consenting patients who presented at a fertility clinic for semen diagnostics. Each sample was split to perform DGC and microfluidic sperm selection (one-step sperm selection with 15 min of incubation) side-by-side. Outcomes evaluated included concentration, progressive motility, and DNA fragmentation index (DFI) of raw semen, and sperm isolated using DGC and the microfluidic device.
Department of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.
DNA interstrand cross-links (ICLs) are the sources of the cytotoxicity of many anticancer agents. Selenium compounds showed great potential as anticancer drugs. In this work, we synthesized a binaphthalene analog containing phenyl selenide (-SePh) as the leaving group and investigated its photochemical reactivity toward DNA as well as its cytotoxicity and selectivity.
Radiation therapy (RT) is one of the core therapies for current cancer management. However, the emergence of radioresistance has become a major cause of radiotherapy failure and disease progression. Therefore, overcoming radioresistance to achieve highly effective treatment for refractory tumors is significant yet challenging.
Chromatin is a dynamic polymer in constant motion. These motions are heterogeneous between cells and within individual cell nuclei and are profoundly altered in response to DNA damage. The shifts in chromatin motions following genomic insults depend on the temporal and physical scales considered.
