DNL4/YOR005C Summary Help

Standard Name DNL4 1
Systematic Name YOR005C
Alias LIG4 2 , 3
Feature Type ORF, Verified
Description DNA ligase required for nonhomologous end-joining (NHEJ), forms stable heterodimer with required cofactor Lif1p, interacts with Nej1p; involved in meiosis, not essential for vegetative growth (1, 3, 4, 5, 6 and see Summary Paragraph)
Name Description DNA Ligase 1
Chromosomal Location
ChrXV:337343 to 334509 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All DNL4 GO evidence and references
  View Computational GO annotations for DNL4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Mutant phenotypes All DNL4 Phenotype evidence and references
Classical genetics
null
Large-scale survey
null
Resources
interactions All DNL4 Interaction evidence and references
63 total interaction(s) for 47 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 16
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 4
  • Co-crystal Structure: 1
  • Co-purification: 1
  • Two-hybrid: 9
Genetic Interactions
  • Negative Genetic: 9
  • Phenotypic Enhancement: 7
  • Phenotypic Suppression: 5
  • Positive Genetic: 1
  • Synthetic Growth Defect: 6
  • Synthetic Rescue: 3
Resources
Expression Summary
histogram
Resources
Protein Information All DNL4 Protein evidence and references
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXV:337343 to 334509 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates		 Chromosomal
Coordinates		 Most Recent Updates
Coordinates Sequence
CDS 1..2835 337343..334509 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000005531
SUMMARY PARAGRAPH for DNL4

DNL4 encodes a DNA ligase required for non-homologous end-joining (NHEJ) (1, 3, 2). Dnl4p assembles as part of the NHEJ machinery at sites of double-strand breaks (DSBs) (7, 8, 9). This machinery is required to align and process the DSBs in preparation for ligation by Dnl4p (reviewed in 10, 11). Dnl4p interacts with Lif1p via two BRCT domains in its carboxy-terminus; this interaction is required for the stability and activity of Dnl4p (12, 13, 14). Dnl4p has also been shown to interact with Nej1p, which interacts with Lif1p and is required for NHEJ (15, 16). A homozygous dnl4 null diploid undergoes meiosis and sporulation less efficiently than wild type cells (3). Dnl4p may also play a role in an alternate microhomology-mediated end-joining pathway (17).

S. cerevisiae encodes another DNA ligase, Cdc9p (18). However, Dnl4p and Cdc9p are not redundant. Dnl4p cannot substitute for Cdc9p during DNA replication, nucleotide excision repair, or base excision repair. Likewise, Cdc9p cannot substitute for Dnl4p during non-homologous end-joining (19 and references therein).

Dnl4p is widely conserved and is known as DNA ligase IV in mammals (1, 2, 4). Mutations in human DNA ligase IV that are associated with the NHEJ disease LIG4 syndrome map to the regions where Dnl4p interacts with Lif1p (14).

Last updated: 2007-07-12

References cited on this page View Complete Literature Guide for DNL4
1) Wilson TE, et al.  (1997) Yeast DNA ligase IV mediates non-homologous DNA end joining. Nature 388(6641):495-8
2) Teo SH and Jackson SP  (1997) Identification of Saccharomyces cerevisiae DNA ligase IV: involvement in DNA double-strand break repair. EMBO J 16(15):4788-95
3) Schar P, et al.  (1997) A newly identified DNA ligase of Saccharomyces cerevisiae involved in RAD52-independent repair of DNA double-strand breaks. Genes Dev 11(15):1912-24
4) Ramos W, et al.  (1998) Biochemical and genetic characterization of the DNA ligase encoded by Saccharomyces cerevisiae open reading frame YOR005c, a homolog of mammalian DNA ligase IV. Nucleic Acids Res 26(24):5676-83
5) Frank-Vaillant M and Marcand S  (2001) NHEJ regulation by mating type is exercised through a novel protein, Lif2p, essential to the ligase IV pathway. Genes Dev 15(22):3005-12
6) Liti G and Louis EJ  (2003) NEJ1 prevents NHEJ-dependent telomere fusions in yeast without telomerase. Mol Cell 11(5):1373-8
7) Chen L, et al.  (2001) Promotion of Dnl4-catalyzed DNA end-joining by the Rad50/Mre11/Xrs2 and Hdf1/Hdf2 complexes. Mol Cell 8(5):1105-15
8) Tseng HM and Tomkinson AE  (2004) Processing and joining of DNA ends coordinated by interactions among Dnl4/Lif1, Pol4, and FEN-1. J Biol Chem 279(46):47580-8
9) Zhang Y, et al.  (2007) Role of Dnl4-Lif1 in nonhomologous end-joining repair complex assembly and suppression of homologous recombination. Nat Struct Mol Biol 14(7):639-46
10) Daley JM, et al.  (2005) Nonhomologous end joining in yeast. Annu Rev Genet 39():431-51
11) Hefferin ML and Tomkinson AE  (2005) Mechanism of DNA double-strand break repair by non-homologous end joining. DNA Repair (Amst) 4(6):639-48
12) Herrmann G, et al.  (1998) Saccharomyces cerevisiae LIF1: a function involved in DNA double-strand break repair related to mammalian XRCC4. EMBO J 17(14):4188-98
13) Teo SH and Jackson SP  (2000) Lif1p targets the DNA ligase Lig4p to sites of DNA double-strand breaks. Curr Biol 10(3):165-8
14) Dore AS, et al.  (2006) Structure of an Xrcc4-DNA ligase IV yeast ortholog complex reveals a novel BRCT interaction mode. DNA Repair (Amst) 5(3):362-8
15) Kegel A, et al.  (2001) Nej1p, a cell type-specific regulator of nonhomologous end joining in yeast. Curr Biol 11(20):1611-7
16) Deshpande RA and Wilson TE  (2007) Modes of interaction among yeast Nej1, Lif1 and Dnl4 proteins and comparison to human XLF, XRCC4 and Lig4. DNA Repair (Amst) 6(10):1507-16
17) Ma JL, et al.  (2003) Yeast Mre11 and Rad1 proteins define a Ku-independent mechanism to repair double-strand breaks lacking overlapping end sequences. Mol Cell Biol 23(23):8820-8
18) Willer M, et al.  (1999) The yeast CDC9 gene encodes both a nuclear and a mitochondrial form of DNA ligase I. Curr Biol 9(19):1085-94
19) Wu X, et al.  (1999) DNA ligation during excision repair in yeast cell-free extracts is specifically catalyzed by the CDC9 gene product. Biochemistry 38(9):2628-35