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
