Biomaterial Database

Identification of Saccharomyces cerevisiae DNA ligase IV: involvement in DNA double-strand break repair. 1997

S H Teo, and S P Jackson

Wellcome/CRC Institute and Department of Zoology, University of Cambridge, UK. sht@mole.bio.cam.ac.uk

DNA ligases catalyse the joining of single and double-strand DNA breaks, which is an essential final step in DNA replication, recombination and repair. Mammalian cells have four DNA ligases, termed ligases I-IV. In contrast, other than a DNA ligase I homologue (encoded by CDC9), no other DNA ligases have hitherto been identified in Saccharomyces cerevisiae. Here, we report the identification and characterization of a novel gene, LIG4, which encodes a protein with strong homology to mammalian DNA ligase IV. Unlike CDC9, LIG4 is not essential for DNA replication, RAD52-dependent homologous recombination nor the repair of UV light-induced DNA damage. Instead, it encodes a crucial component of the non-homologous end-joining (NHEJ) apparatus, which repairs DNA double-strand breaks that are generated by ionizing radiation or restriction enzyme digestion: a function which cannot be complemented by CDC9. Lig4p acts in the same DNA repair pathway as the DNA end-binding protein Ku. However, unlike Ku, it does not function in telomere length homeostasis. These findings indicate diversification of function between different eukaryotic DNA ligases. Furthermore, they provide insights into mechanisms of DNA repair and suggest that the NHEJ pathway is highly conserved throughout the eukaryotic kingdom.

UI	MeSH Term	Description	Entries
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010802	Phylogeny	The relationships of groups of organisms as reflected by their genetic makeup.	Community Phylogenetics,Molecular Phylogenetics,Phylogenetic Analyses,Phylogenetic Analysis,Phylogenetic Clustering,Phylogenetic Comparative Analysis,Phylogenetic Comparative Methods,Phylogenetic Distance,Phylogenetic Generalized Least Squares,Phylogenetic Groups,Phylogenetic Incongruence,Phylogenetic Inference,Phylogenetic Networks,Phylogenetic Reconstruction,Phylogenetic Relatedness,Phylogenetic Relationships,Phylogenetic Signal,Phylogenetic Structure,Phylogenetic Tree,Phylogenetic Trees,Phylogenomics,Analyse, Phylogenetic,Analysis, Phylogenetic,Analysis, Phylogenetic Comparative,Clustering, Phylogenetic,Community Phylogenetic,Comparative Analysis, Phylogenetic,Comparative Method, Phylogenetic,Distance, Phylogenetic,Group, Phylogenetic,Incongruence, Phylogenetic,Inference, Phylogenetic,Method, Phylogenetic Comparative,Molecular Phylogenetic,Network, Phylogenetic,Phylogenetic Analyse,Phylogenetic Clusterings,Phylogenetic Comparative Analyses,Phylogenetic Comparative Method,Phylogenetic Distances,Phylogenetic Group,Phylogenetic Incongruences,Phylogenetic Inferences,Phylogenetic Network,Phylogenetic Reconstructions,Phylogenetic Relatednesses,Phylogenetic Relationship,Phylogenetic Signals,Phylogenetic Structures,Phylogenetic, Community,Phylogenetic, Molecular,Phylogenies,Phylogenomic,Reconstruction, Phylogenetic,Relatedness, Phylogenetic,Relationship, Phylogenetic,Signal, Phylogenetic,Structure, Phylogenetic,Tree, Phylogenetic
D011088	DNA Ligases	Poly(deoxyribonucleotide):poly(deoxyribonucleotide)ligases. Enzymes that catalyze the joining of preformed deoxyribonucleotides in phosphodiester linkage during genetic processes during repair of a single-stranded break in duplex DNA. The class includes both EC 6.5.1.1 (ATP) and EC 6.5.1.2 (NAD).	DNA Joinases,DNA Ligase,Polydeoxyribonucleotide Ligases,Polydeoxyribonucleotide Synthetases,T4 DNA Ligase,DNA Ligase, T4,Joinases, DNA,Ligase, DNA,Ligase, T4 DNA,Ligases, DNA,Ligases, Polydeoxyribonucleotide,Synthetases, Polydeoxyribonucleotide
D004249	DNA Damage	Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.	DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004260	DNA Repair	The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones.	DNA Damage Response
D004271	DNA, Fungal	Deoxyribonucleic acid that makes up the genetic material of fungi.	Fungal DNA
D005800	Genes, Fungal	The functional hereditary units of FUNGI.	Fungal Genes,Fungal Gene,Gene, Fungal
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072481	DNA Ligase ATP	ATP-dependent cellular enzyme which catalyzes DNA replication, repair and recombination through formation of internucleotide ester bonds between phosphate and deoxyribose moieties. Vertebrate cells encode three well-characterized DNA ligases, DNA ligase I, III and IV, all of which are related in structure and sequence. DNA ligases either require ATP or NAD. However, archaebacterial, viral, and some eubacterial DNA ligases are ATP-dependent.	ATP-Dependent DNA Ligase,DNA Ligase I,DNA Ligase II,DNA Ligase III,DNA Ligase IIIalpha,DNA Ligase IV,DNA Ligases, ATP-Dependent,LIGIIIalpha Protein,Polydeoxyribonucleotide Synthase ATP,ATP Dependent DNA Ligase,ATP, DNA Ligase,ATP, Polydeoxyribonucleotide Synthase,ATP-Dependent DNA Ligases,DNA Ligase, ATP-Dependent,DNA Ligases, ATP Dependent,IIIalpha, DNA Ligase,Ligase ATP, DNA,Ligase I, DNA,Ligase II, DNA,Ligase III, DNA,Ligase IIIalpha, DNA,Ligase IV, DNA,Ligase, ATP-Dependent DNA,Ligases, ATP-Dependent DNA,Synthase ATP, Polydeoxyribonucleotide
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein