Work

Faculty Opinions recommendation of Targeted and Persistent 8-Oxoguanine Base Damage at Telomeres Promotes Telomere Loss and Crisis.

Year: 2019

Type: peer-review

Abstract: Telomeres are essential for genome stability.Oxidative stress caused by excess reactive oxygen species (ROS) accelerates telomere shortening.Although telomeres are hypersensitive to ROSmediated 8-oxoguanine (8-oxoG) formation, the biological effect of this common lesion at telomeres is poorly understood because ROS have pleiotropic effects.Here we developed a chemoptogenetic tool that selectively produces 8-oxoG only at telomeres.Acute telomeric 8-oxoG formation increased telomere fragility in cells lacking OGG1, the enzyme that removes 8-oxoG, but did not compromise cell survival.However, chronic telomeric 8-oxoG induction over time shortens telomeres and impairs cell growth.Accumulation of telomeric 8-oxoG in chronically exposed OGG1-deficient cells triggers replication stress, as evidenced by mitotic DNA synthesis at

Source: Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature

DOI: 10.3410/f.735786589.793562218

Author: Jerry Shay

Institution: The University of Texas Southwestern Medical Center

Language: English

Topic: Telomeres, Telomerase, and Senescence

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Cancer Institute, National Institute of Environmental Health Sciences