Cockayne syndrome mutation in XPG activate the integrated stress response.

ABSTRACT: Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are diseases provoked by mutations in multifunctional proteins that are involved in DNA repair. DNA-repair deficiency explains the high cancer incidence of XP, whereas cancer-free CS, characterized by growth retardation, neurological degeneration, and premature aging does not present as a classical DNA-repair deficiency disorder. Here, we compared a severe combined XP/CS case provoked by XPG-mutation with an XP "only" patient cell line caused by mutation in the same XPG gene to carve out the pathogenic cellular disturbances that provoke CS. We identified RNA polymerase I transcription and rRNA maturation defects, a highly phosphorylated eukaryotic initiation factor 2 alpha (eIF2alpha), and a shift from cap- to internal ribosomal entry s

SUBMITTER: Zhang D 

PROVIDER: S-EPMC12823737 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature