Defective embryonic neurogenesis in Ku-deficient but not DNA-dependent protein kinase catalytic subunit-deficient mice

Yansong Gu, Jo Ann Sekiguchi, Yijie Gao, Pieter Dikkes, Karen Frank, David Ferguson, Paul Hasty, Jerold Chun, Frederick W. Alt

Research output: Contribution to journalArticlepeer-review

160 Scopus citations

Abstract

Mammalian nonhomologous DNA end joining employs Ku70, Ku80, DNA- dependent protein kinase catalytic subunit (DNA-PKcs), XRCC4, and DNA ligase IV (Lig4). Herein, we show that Ku70 and Ku80 deficiency but not DNA-PKcs deficiency results in dramatically increased death of developing embryonic neurons in mice. The Ku-deficient phenotype is qualitatively similar to, but less severe than, that associated with XRCC4 and Lig4 deficiency. The lack of a neuronal death phenotype in DNA-PKcs-deficient embryos and the milder phenotype of Ku-deficient versus XRCC4- or Lig4-deficient embryos correlate with relative leakiness of residual end joining in these mutant backgrounds as assayed by a V(D)J recombination end joining assay. We conclude that normal development of the nervous system depends on the four evolutionarily conserved nonhomologous DNA end joining factors.

Original languageEnglish (US)
Pages (from-to)2668-2673
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number6
DOIs
StatePublished - Mar 14 2000

ASJC Scopus subject areas

  • General

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