DNA ligase

spinqualitylabelsall models ATP-dependent DNA ligase complexed with ATP 2hix Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D File:2hix.png Crystal Structure of DNA ligase 2hix DNA ligase (LigD) is an enzyme which repairs single-stranded breaks in a double-stranded DNA. LigD is activated , in a species-dependent manner, by hydrolysis of ATP or NAD+. Mammalian LigD I ligates the nascent DNA of the lagging strand; LigD III complexes with XRCC1 in the process of nucleotide excision repair; LigD IV complexes with XRCC4 and catalyzes the last step in the non-homologous DNA end joining. Disease Known disease associated with this structure: DNA ligase I deficiency OMIM:[126391] The expression of DNA ligase I has been directly linked to cancer in humans. The enzyme is found most in proliferating cells and much less often in nondividing cells. In particular, in malignant tumors, the DNA ligase I enzyme was expressed much more compared to the DNA ligase I enzyme in normal tissues and their peripheral lymphocytes. Further experimentation showed that tumor cell growth rate was successfully decreased when antisense oligonucleotides targeting the mRNA of DNA ligase I were present. This suggests that DNA ligase I could be a good target for new anticancer studies. A specific point mutation (46BR in the mouse Lig1 gene) in DNA ligase I has also been linked as a cause for genome instability and cancer in humans. One possible reason for this is the accumulation of DNA fragments that are no longer ligated by the mutant DNA ligase I enzyme. 3D Structures of DNA ligase Update June 2012 ATP-dependent LigD 3p4h, 3ta5, 3ta7 – LigD N-terminal – Candidatus korarchaeum cryptofilum 3gde – LigD – Archaeoglobus fulgidus 2hiv – SsLigD – Sulfolobus solfataricus 2hix - SsLigD + ATP 2cfm - LigD + AMP – Pyrococcus furiosus 2fao - PaLigD polymerase domain – Pseudomonas aeruginosa 2faq, 2far - PaLigD polymerase domain + ATP + Mn 1a0i – LigD + ATP – Bacteriophage T7 4eq5 – LigD + AMP – Thermococcus sibiricus NAD+-dependent LigD 3jsl, 3jsn - LigD adenylation domain – Staphylococcus aureus 3ba8, 3ba9, 3baa, 3bab, 3bac - EfLigD adenylation domain + inhibitor – Enterococcus faecalis 1ta8, 1tae - EfLigD adenylation domain 1zau - LigD adenylation domain – Mycobacterium tuberculosis 1v9p, 1dgs – LigD – Thermos filiformis 1b04 – LigD adenylation domain (mutant) – Geobacillus stearothermophilus LigD 2q2t – CvLigD + DNA + AMP + CMP – Chlorella virus 2q2u, 1p8l, 1fvi - CvLigD + DNA + mononucleotide 2owo – LigD + DNA + AMP + CMP – Escherichia coli 3qwu – LigD – Aquifex aeolicus 3pn1 – HiLigD adenylation domain + inhibitor – Haemophilus influenzae 3uq8 - HiLigD adenylation domain + NAD 1l7b – LigD BRCT domain – Thermos thermophilus - NMR 3rr5 – LigD - Thermococcus Mammalian LigD I 1x9n – hLigD I + DNA + AMP + CMP – human 2od8 – LigD I residues 32-53 + PCNA Mammalian LigD III 3l2p – hLigD III residues 257-833 + DNA 1uw0 - hLigD III zinc-finger domain residues 1-117 – NMR 1imo, 1in1 - hLigD III BRCTdomain – NMR 3pc7 - hLigD III BRCTdomain 3pc8 - hLigD III BRCTdomain (mutant) + XRCC1 3qvg - hLigD III BRCTdomain + XRCC1 Mammalian LigD IV 3ii6, 1ik9 – hLigD IV C-terminal BRCT domains + DNA repair protein XRCC4 2e2w - hLigD IV BRCT domain - NMR 1z56 – LigD IV + ligase interacting factor 1 - yeast

REFERENCES

Elevated expression of DNA ligase I in human cancers., Sun DY, Urrabaz R, Nguyen M, Marty J, Stringer S, Cruz E, Medina-Gundrum L, Weitman S., Clinical Cancer Research. 2001; 7(12):4143-4148.
Replication failure, genome instability, and increased cancer susceptibility in mice with a point mutation in the DNA ligase I gene., Harrison C, Ketchen AM, Redhead NJ, O'Sullivan MJ, Melton DW., Cancer Research. 2002; 62(14):4065-4074.

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