Inherited C-Terminal TREX1 Variants Disrupt Homology-Directed Repair to Cause Senescence and DNA Damage Phenotypes in Drosophila, Mice, and Humans

Inherited C-terminal TREX1 variants disrupt homology-directed repair to cause senescence and DNA damage phenotypes in Drosophila, mice, and humans

Age-related microangiopathy, also known as small vessel disease (SVD), causes damage to the brain, retina, liver, and kidney. Based on the DNA damage theory of aging, we reasoned that genomic instability may underlie an SVD caused by dominant C-terminal variants in TREX1, the most abundant 3′−5′ DNA exonuclease in mammals. C-terminal TREX1 variants cause an adult-onset SVD known as retinal vasculopathy with cerebral leukoencephalopathy (RVCL or …

Faulty DNA Repair Mechanism in DIAL Syndrome Raises Childhood Cancer Risk

Researchers from the University of Birmingham, U.K., have identified a new inherited disease that affects a person’s ability to repair DNA, elevating the risk of developing blood cancer and preventing the repair of damage caused to DNA by common chemotherapy regimens. The newly characterized DIAL (DIAPH1 Loss-of-function) syndrome affects the body’s ability to perform homologous recombination (HR), a form of DNA repair critical for genome stabil…

New Inherited Disorder Impairs DNA Repair and Raises Cancer Risk

A new hereditary condition has been discovered that affects patients' ability to repair DNA – leaving them both at greater risk of developing blood cancer, and unable to repair some of the damage caused by chemotherapy treatments.