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Genes and Development
Vol. 11, No. 15,
pp. 1912-1924,
August 1, 1997
Imperial Cancer Research Fund, Clare Hall Laboratories,
South Mimms, UK
Eukaryotic DNA ligases are ATP-dependent DNA strand-joining
enzymes that participate in DNA replication, repair, and recombination. Whereas mammalian cells contain several different DNA ligases, encoded
by at least three distinct genes, only one DNA ligase has been detected
previously in either budding yeast or fission yeast. Here, we describe
a newly identified nonessential Saccharomyces cerevisiae gene
that encodes a DNA ligase distinct from the CDC9 gene product. This DNA
ligase shares significant amino acid sequence homology with human DNA
ligase IV; accordingly, we designate the yeast gene LIG4.
Recombinant LIG4 protein forms a covalent enzyme-AMP complex and can
join a DNA single-strand break in a DNA/RNA hybrid duplex, the preferred substrate in vitro. Disruption of the
LIG4 gene causes only marginally increased cellular sensitivity
to several DNA damaging agents, and does not further sensitize
cdc9 or rad52 mutant cells. In contrast, lig4
mutant cells have a 1000-fold reduced capacity for correct
recircularization of linearized plasmids by illegitimate end-joining
after transformation. Moreover, homozygous lig4 mutant diploids
sporulate less efficiently than isogenic wild-type cells, and show
retarded progression through meiotic prophase I. Spore viability is
normal, but lig4 mutants appear to produce a higher proportion
of tetrads with only three viable spores. The mutant phenotypes are
consistent with functions of LIG4 in an illegitimate DNA end-joining
pathway and ensuring efficient meiosis.
[Key Words: DNA repair; illegitimate recombination; meiosis; DNA ligase IV; CDC9]
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