SMCHD1 Promotes ATM-dependent DNA Damage Signaling and Repair of Uncapped Telomeres

ABSTRACT: Structural maintenance of chromosomes flexible hinge domain-containing protein 1 (SMCHD1) has been implicated in X-chromosome inactivation, imprinting, and DNA damage repair, and mutations in SMCHD1 can cause facioscapulohumoral muscular dystrophy. More recently, SMCHD1 has also been identified as a component of telomeric chromatin. Here, we report that SMCHD1 is required for DNA damage signaling and non-homologous end joining (NHEJ) at unprotected telomeres. Co-depletion of SMCHD1 and the shelterin subunit TRF2 reduced telomeric 3'-overhang removal in time-course experiments, as well as the number of chromosome end fusions. SMCHD1-deficient cells displayed reduced ATM S1981 phosphorylation and diminished formation of ?H2AX foci and of 53BP1-containing telomere dysfunction-induced foci (TI

SUBMITTER: Dr. Alexandra Vancevska 

PROVIDER: S-SCDT-EMBOJ-2019-102668 | biostudies-other |

REPOSITORIES: biostudies-other