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Sez4 gene encoding an elongation subunit of DNA polymerase ζ is required for normal embryogenesis
Author(s) -
Kajiwara Kagemasa,
OWang Jiyang,
Sakurai Takayuki,
Yamashita Shunji,
Tanaka Masafumi,
Sato Masahiro,
Tagawa Masatoshi,
Sugaya Eiichi,
Nakamura Kenji,
Nakao Kazuki,
Katsuki Motoya,
Kimura Minoru
Publication year - 2001
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1365-2443.2001.00410.x
Subject(s) - biology , gene , elongation , protein subunit , embryogenesis , dna polymerase , microbiology and biotechnology , dna , polymerase , genetics , computational biology , materials science , ultimate tensile strength , metallurgy
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 ζ 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 ζ 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 ζ in the survival of certain subcellular populations which are indispensable to normal embryogenesis.