| First Author | Akhter S | Year | 2010 |
| Journal | Aging Cell | Volume | 9 |
| Issue | 6 | Pages | 1047-56 |
| PubMed ID | 20854421 | Mgi Jnum | J:217052 |
| Mgi Id | MGI:5612958 | Doi | 10.1111/j.1474-9726.2010.00631.x |
| Citation | Akhter S, et al. (2010) The telomeric protein SNM1B/Apollo is required for normal cell proliferation and embryonic development. Aging Cell 9(6):1047-56 |
| abstractText | Conserved metallo beta-Lactamase and beta-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. |
