Loss of ATM causes R-loop-associated transcriptional dysregulation and attenuates the related response to DNA damage.

ABSTRACT: An early childhood onset neurodegenerative disorder, ataxia telangiectasia (AT), affects one in 40,000 to 100,000 individuals worldwide and is caused by mutations in the ataxia telangiectasia mutated (ATM) threonine-serine kinase, which regulates the DNA damage response (DDR). While the cause of AT has been known for years, the exact molecular mechanisms underlying disease progression, particularly at the transcriptomic level, remain poorly understood. Three stranded structures, known as R-loops, have recently emerged as important players in the DDR via regulating key gene expression. Here, we utilized neuronal progenitor cells (NPCs) derived from induced pluripotent stem cells reprogrammed from patient-derived somatic cells to identify how loss of ATM impacts R-loop and transcriptional dy

SUBMITTER: Westover KR 

PROVIDER: S-EPMC12906170 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature