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Pontin is a highly conserved DNA helicase/ATPase which is a component of several macromolecular complexes with functions that include DNA repair, telomere maintenance and tumor suppression. While Pontin is known to be essential in yeast, fruit flies and frogs, its physiological role in mammalian organisms remains to be determined. We here find that Pontin is highly expressed in embryonic stem cells and hematopoietic tissues. Through germline inactivation of Ruvbl1, the gene encoding Pontin, we found it to be essential for early embryogenesis, as Ruvbl1 null embryos could not be recovered beyond the blastocyst stage where proliferation of the pluripotent inner cell mass was impaired. Conditional ablation of Ruvbl1 in hematopoietic tissues led to bone marrow failure. Competitive repopulation experiments showed that this included the loss of hematopoietic stem cells through apopotosis. Pontin is, therefore, essential for the function of both embryonic pluripotent cells and adult hematopoietic stem cells.

Original publication

DOI

10.3324/haematol.2011.060251

Type

Journal article

Journal

Haematologica

Publication Date

09/2012

Volume

97

Pages

1291 - 1294

Keywords

ATPases Associated with Diverse Cellular Activities, Animals, Apoptosis, Blotting, Western, Bone Marrow, Cell Differentiation, Cell Survival, Cells, Cultured, DNA Helicases, Embryonic Stem Cells, Flow Cytometry, Hematopoietic Stem Cells, Integrases, Mice, Mice, Knockout, Phenotype