Yeast DNA ligase IV mediates non-homologous DNA end joining

  title={Yeast DNA ligase IV mediates non-homologous DNA end joining},
  author={Thomas E. Wilson and Ulf Grawunder and Michael R Lieber},
The discovery of homologues from the yeast Saccharomyces cerevisiae of the human Ku DNA-end-binding proteins (HDF1 and KU80) has established that this organism is capable of non-homologous double-strand end joining (NHEJ), a form of DNA double-strand break repair (DSBR) active in mammalian V(D)J recombination. Identification of the DNA ligase that mediates NHEJ in yeast will help elucidate the function of the four mammalian DNA ligases in DSBR, V(D)J recombination and other reactions. Here we… 

Saccharomyces cerevisiae DNA Ligase IV Supports Imprecise End Joining Independently of Its Catalytic Activity

Findings indicate that Dnl4 can promote mutagenic end joining independently of its catalytic activity, likely by a mechanism that involves Cdc9.

Identification of genes involved in repair of DNA double-strand breaks in mammalian cells.

The evidence implicating four proteins as functioning in NHEJ is reviewed and their properties and role in other pathways are discussed and the significance of DSB repair to clinical radiosensitivity and human disorders is evaluated.

Completion of base excision repair by mammalian DNA ligases.

Saccharomyces cerevisiae LIF 1 : a function involved in DNA double-strand break repair related to mammalian XRCC 4

The discovery of LIF1, a S.cerevisiae protein that strongly interacts with the C-terminal BRCT domain of yeast LIG4, allows for mutational analyses of structure–function relationships in XRCC4-like proteins to define their role in DNA double-strand break repair.

Arabidopsis DNA ligase IV is induced by gamma-irradiation and interacts with an Arabidopsis homologue of the double strand break repair protein XRCC4.

An Arabidopsis thaliana homologue (AtLIG4) of human and S. cerevisiaeDNA ligase IV is identified which is shown to encode an ATP-dependent DNA ligase with a theoretical molecular mass of 138 kDa and 48% similarity in amino-acid sequence to the human DNA ligasing protein XRCC4.

Genetic evidence for the involvement of DNA ligase IV in the DNA-PK-dependent pathway of non-homologous end joining in mammalian cells.

End joining in vitro is dominated by pathways with properties similar to B-NHEJ that do not display a strong dependence on DNA ligase IV, with D-N HEJ retaining only a limited contribution.

Conserved interactions of the splicing factor Ntr1/Spp382 with proteins involved in DNA double-strand break repair and telomere metabolism

Interactions of the DNA ligase IV-associated proteins Lif1p and XRCC4 of yeast and human with the putatively orthologous G-patch proteins Ntr1p/Spp382p and NTR1/TFIP11 that have recently been implicated in mRNA splicing are described.



The Saccharomyces cerevisiae Ku autoantigen homologue affects radiosensitivity only in the absence of homologous recombination.

The results give further support to the notion that, in contrast to higher eukaryotic cells, homologous recombination is the favored pathway of double-strand break repair in yeast whereas other competing mechanisms such as the suggested pathway of DNA-PK-dependent direct break rejoining are only of minor importance.

DNA ligase I from Saccharomyces cerevisiae: physical and biochemical characterization of the CDC9 gene product.

The ability of Cdc9 DNA ligase to join nicks with mismatches at the termini had very little effect on ligation, whereas mismatches opposite a purine at 3' termini inhibited DNA ligation.

Activity of DNA ligase IV stimulated by complex formation with XRCC4 protein in mammalian cells

It is shown that DNA ligase IV co-immunoprecipitates with XRCC4 and that these two proteins specifically interact with one another in a yeast two-hybrid system and concludes that the biological consequences of mutating XR CC4 are primarily due to the loss of its stimulatory effect on DNA ligases IV.

Mutations in two Ku homologs define a DNA end-joining repair pathway in Saccharomyces cerevisiae

A Saccharomyces cerevisiae gene (KU80) is discovered that is structurally similar to the 80-kDa mammalian Ku subunit, and Ku and Rad50 participate in an end-joining pathway that is distinct from homologous recombinational repair.

Identification of a Saccharomyces cerevisiae Ku80 homologue: roles in DNA double strand break rejoining and in telomeric maintenance.

The identification and characterisation of YKU80, the gene for the Saccharomyces cerevisiae Ku80 homologue, are described and it is reported that yku80 mutant yeasts display dramatic telomeric shortening, suggesting that, in addition to recognising DNA damage, Ku also binds to naturally occurring chromosomal ends.

The nucleotide sequence of the DNA ligase gene (CDC9) from Saccharomyces cerevisiae: a gene which is cell-cycle regulated and induced in response to DNA damage.

The CDC9 gene of Saccharomyces cerevisiae encodes a DNA ligase, and the nucleotide sequence of a 3.85 kb fragment of DNA which encompasses the convergently transcribed CDC9 and CDC36 genes is determined, implying that these two genes are transcribed from overlapping sequences.

Incision and postincision steps of pyrimidine dimer removal in excision-defective mutants of Saccharomyces cerevisiae

In strains containing excision-defective mutations in any of nine genes in combination with the cdc9 mutation, the absence ofLow-molecular-weight DNA at the nonpermissive temperature after ultraviolet treatment suggests that these mutants are incision defective, whereas the presence of low-molescular- Weight DNA indicates that the mutants are defective in a step after incision.

Recognition and processing of damaged DNA

A family of four distinct DNA ligases in human cell nuclei is found, whereas only a single DNA ligase has been detected in yeast, suggesting that the cellular responses to DNA strand breaks may differ markedly between higher and lower eukaryotes.

Molecular cloning and expression of human cDNAs encoding a novel DNA ligase IV and DNA ligase III, an enzyme active in DNA repair and recombination

Four DNA ligases have been purified from human cells and shown to be identical to the 96-kDa DNA ligase by unique agreement between mass spectrometry data on tryptic peptides from the purified enzyme and the predicted open reading frame of the cloned cDNA.

Saccharomyces cerevisiae Ku70 potentiates illegitimate DNA double‐strand break repair and serves as a barrier to error‐prone DNA repair pathways.

It is shown that the simple inactivation of the Saccharomyces cerevisiae Ku70 homologue (Yku70p), does not lead to increased radiosensitivity, and studies suggest that Yku70 promotes genomic stability both by promoting accurate DNA repair and by serving as a barrier to error‐prone repair processes.