Telomere dysfunction implicates POT1 in patients with idiopathic pulmonary fibrosis.
J Exp Med
; 219(5)2022 05 02.
Article
em En
| MEDLINE
| ID: mdl-35420632
ABSTRACT
Exonic sequencing identified a family with idiopathic pulmonary fibrosis (IPF) containing a previously unreported heterozygous mutation in POT1 p.(L259S). The family displays short telomeres and genetic anticipation. We found that POT1(L259S) is defective in binding the telomeric overhang, nuclear accumulation, negative regulation of telomerase, and lagging strand maintenance. Patient cells containing the mutation display telomere loss, lagging strand defects, telomere-induced DNA damage, and premature senescence with G1 arrest. Our data suggest POT1(L259S) is a pathogenic driver of IPF and provide insights into gene therapy options.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Telomerase
/
Fibrose Pulmonar Idiopática
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article