POLD3 is haploinsufficient for DNA replication in mice

Article Article scientifique Article POLD3 is haploinsufficient for DNA replication in mice eng 2016-09 author Murga Matilde author Lecona Emilio 0000-0002-1687-2562 author Kamileri Irene author Díaz Marcos author Lugli Natalia 706163 author Sotiriou Sotirios 730065 author Anton Marta E. author Sanchez Mendez Juan Pedro 735654 author Halazonetis Thanos 641033 Département de biologie moléculaire et cellulaire (MOCEL) author Fernandez-Capetillo Oscar 0000-0002-2690-6885 877-883 10.1016/j.molcel.2016.07.007 27524497 1097-2765 PMC5029548 https://linkinghub.elsevier.com/retrieve/pii/S1097276516303343 <p>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.</p> Dewey 570 Howard Hughes Medical Institute European Research Council 617840 7daed2ee-1311-4824-9df9-2e51260a966a Département de biologie moléculaire et cellulaire 16484 false Molecular cell 63 5 e2e4bf04-6941-4945-b6a4-58a0627e0d90 Article (Published version) Public HALAZONETIS09.pdf 1805594 application/pdf OA OTHER b72988bb519a5d607fb42e4106ba40a0f3f9c3f29abebfb7ac432606d27e3431 openAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire et cellulaire

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POLD3 is haploinsufficient for DNA replication in mice	Molecular cell			2016	85	134

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Sanchez Mendez, Juan Pedro