Sez4 gene encoding an elongation subunit of DNA polymerase zeta is required for normal embryogenesis.
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.


CONCLUSIONS
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.
Molecular Medicine Research Center, The Institute of Medical Sciences, Tokai University, Isehara, Kanagawa 259-1193, Japan. kagemasa@is.icc.u-tokai.ac.jp
K
K
Kajiwara
J
J
O-Wang
T
T
Sakurai
S
S
Yamashita
M
M
Tanaka
M
M
Sato
M
M
Tagawa
E
E
Sugaya
K
K
Nakamura
K
K
Nakao
M
M
Katsuki
M
M
Kimura
D000818:Animals; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005822:Genetic Vectors; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D019076:Transgenes
D012333:RNA, Messenger; D004259:DNA-Directed DNA Polymerase