BACKGROUND: Sez4 identified as a seizure-activated gene shows a similarity to the yeast REV3 that encodes a catalytic subunit of the nonessential DNA polymerase zeta which is involved in error-prone translesion synthesis. Although yeast REV3 homologues in mouse and human have recently been identified and characterized, their precise roles remain elusive. RESULTS: Here we investigated the role of mouse pol zeta by targeted inactivation of the Sez4 gene. The homozygous Sez4 mutants died around embryonic day (E) 10.5. This lethal effect was the result of developmental defects and apoptotic cell death within the embryo proper at the gastrulation stage, and it was partially rescued at E12.5 by the expression of a Sez4-transgene. In wild-type embryos, Sez4 transcripts were up-regulated within the embryo proper from E7.5, correlating well with the lethal stage of Sez4-inactivation. CONCLUSION: Our findings indicate that Sez4 is essential for epiblast lineage-specific development and suggests a requirement of mammalian DNA polymerase zeta in the survival of certain subcellular populations which are indispensable to normal embryogenesis.
BACKGROUND:Sez4 identified as a seizure-activated gene shows a similarity to the yeastREV3 that encodes a catalytic subunit of the nonessential DNA polymerase zeta which is involved in error-prone translesion synthesis. Although yeastREV3 homologues in mouse and human have recently been identified and characterized, their precise roles remain elusive. RESULTS: Here we investigated the role of mouse pol zeta by targeted inactivation of the Sez4 gene. The homozygous Sez4 mutants died around embryonic day (E) 10.5. This lethal effect was the result of developmental defects and apoptotic cell death within the embryo proper at the gastrulation stage, and it was partially rescued at E12.5 by the expression of a Sez4-transgene. In wild-type embryos, Sez4 transcripts were up-regulated within the embryo proper from E7.5, correlating well with the lethal stage of Sez4-inactivation. CONCLUSION: Our findings indicate that Sez4 is essential for epiblast lineage-specific development and suggests a requirement of mammalian DNA polymerase zeta in the survival of certain subcellular populations which are indispensable to normal embryogenesis.
Authors: Petra P H Van Sloun; Isabelle Varlet; Edwin Sonneveld; Jan J W A Boei; Ron J Romeijn; Jan C J Eeken; Niels De Wind Journal: Mol Cell Biol Date: 2002-04 Impact factor: 4.272
Authors: Reeja S Maskey; Myoung Shin Kim; Darren J Baker; Bennett Childs; Liviu A Malureanu; Karthik B Jeganathan; Yuka Machida; Jan M van Deursen; Yuichi J Machida Journal: Nat Commun Date: 2014-12-11 Impact factor: 14.919