TY - JOUR
T1 - Early embryonic lethality due to targeted inactivation of DNA ligase III
AU - Puebla-Osorio, Nahum
AU - Lacey, Devin B.
AU - Alt, Frederick W.
AU - Zhu, Chengming
PY - 2006/5
Y1 - 2006/5
N2 - DNA ligases catalyze the joining of strand breaks in the phospliodiester backbone of duplex DNA and play essential roles in DNA replication, recombination, repair, and maintenance of genomic integrity. Three mammalian DNA ligase genes have been identified, and their corresponding ligases play distinct roles in DNA metabolism. DNA ligase III is proposed to be involved in the repairing of DNA single-strand breaks, but its precise role has not yet been demonstrated directly. To determine its role in DNA repair, cellular growth, and embryonic development, we introduced targeted interruption of the DNA ligase III (LIG3) gene into the mouse. Mice homozygous for LIG3 disruption showed early embryonic lethality. We found that the mutant embryonic developmental process stops at 8.5 days postcoitum (dpc), and excessive cell death occurs at 9.5 dpc. LIG3 mutant cells have relatively normal XRCC1 levels but elevated sister chromatid exchange. These findings indicate that DNA ligase III is involved in essential DNA repair activities required for early embryonic development and therefore cannot be replaced by other DNA ligases.
AB - DNA ligases catalyze the joining of strand breaks in the phospliodiester backbone of duplex DNA and play essential roles in DNA replication, recombination, repair, and maintenance of genomic integrity. Three mammalian DNA ligase genes have been identified, and their corresponding ligases play distinct roles in DNA metabolism. DNA ligase III is proposed to be involved in the repairing of DNA single-strand breaks, but its precise role has not yet been demonstrated directly. To determine its role in DNA repair, cellular growth, and embryonic development, we introduced targeted interruption of the DNA ligase III (LIG3) gene into the mouse. Mice homozygous for LIG3 disruption showed early embryonic lethality. We found that the mutant embryonic developmental process stops at 8.5 days postcoitum (dpc), and excessive cell death occurs at 9.5 dpc. LIG3 mutant cells have relatively normal XRCC1 levels but elevated sister chromatid exchange. These findings indicate that DNA ligase III is involved in essential DNA repair activities required for early embryonic development and therefore cannot be replaced by other DNA ligases.
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U2 - 10.1128/MCB.26.10.3935-3941.2006
DO - 10.1128/MCB.26.10.3935-3941.2006
M3 - Article
C2 - 16648486
AN - SCOPUS:33646589977
SN - 0270-7306
VL - 26
SP - 3935
EP - 3941
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 10
ER -