2026-05-22T00:02:55Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/85272025-05-13T11:16:17Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Murga, Matilde
author
Lecona, Emilio
author
Kamileri, Irene
author
Díaz, Marcos
author
Lugli, Natalia
author
Sotiriou, Sotirios K
author
Anton, Marta E
author
Mendez, Juan
author
Halazonetis, Thanos D
author
Fernandez-Capetillo, Oscar
funder
Botín Foundation
funder
Banco Santander
funder
Ministerio de Economía y Competitividad (España)
funder
Fundación La Marató TV3
funder
Howard Hughes Medical Institute
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
2019-10-23T09:52:04Z
2019-10-23T09:52:04Z
2016-09-01
Mol Cell. 2016;63(5):877-83.
10.1016/j.molcel.2016.07.007
1097-4164
10972765
Molecular cell
27524497
http://hdl.handle.net/20.500.12105/8527
The Pold3 gene encodes a subunit of the Polδ DNA polymerase complex. Pold3 orthologs are not essential in Saccharomyces cerevisiae or chicken DT40 cells, but the Schizosaccharomyces pombe ortholog is essential. POLD3 also has a specialized role in the repair of broken replication forks, suggesting that POLD3 activity could be particularly relevant for cancer cells enduring high levels of DNA replication stress. We report here that POLD3 is essential for mouse development and is also required for viability in adult animals. Strikingly, even Pold3(+/-) mice were born at sub-Mendelian ratios, and, of those born, some presented hydrocephaly and had a reduced lifespan. In cells, POLD3 deficiency led to replication stress and cell death, which were aggravated by the expression of activated oncogenes. Finally, we show that Pold3 deletion destabilizes all members of the Polδ complex, explaining its major role in DNA replication and the severe impact of its deficiency.
eng
POLD3 Is Haploinsufficient for DNA Replication in Mice
journal article
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