Open AccessThe telomeric protein SNM1B/Apollo is required for normal cell proliferation and embryonic development
Author(s) -
Akhter Shamima,
Lam Yung C.,
Chang Sandy,
Legerski Randy J.
Publication year - 2010
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2010.00631.x
Subject(s) - shelterin , biology , apollo , microbiology and biotechnology , embryonic stem cell , knockout mouse , telomere , genetics , transcription factor , dna , dna binding protein , gene , zoology
Summary Conserved metallo β‐Lactamase and β‐CASP (CPSF‐Artemis‐Snm1‐Pso2) domain nuclease family member SNM1B/Apollo is a shelterin‐associated protein that localizes to telomeres through its interaction with TRF2. To study its in vivo role, we generated a knockout of SNM1B/Apollo in a mouse model. Snm1B/Apollo homozygous null mice die at birth with developmental delay and defects in multiple organ systems. Cell proliferation defects were observed in Snm1B/Apollo mutant mouse embryonic fibroblasts (MEFs) owing to high levels of telomeric end‐to‐end fusions. Deficiency of the nonhomologous end‐joining (NHEJ) factor Ku70 , but not p53 , rescued the developmental defects and lethality observed in Snm1B/Apollo mutant mice as well as the impaired proliferation of Snm1B/Apollo ‐deficient MEFs. These findings demonstrate that SNM1B/Apollo is required to protect telomeres against NHEJ‐mediated repair, which results in genomic instability and the consequent multi‐organ developmental failure. Although Snm1B/Apollo ‐deficient MEFs exhibited high levels of apoptosis, abrogation of p53‐dependent programmed cell death did not rescue the multi‐organ developmental failure in the mice.