DNA ligase
From Proteopedia
(Difference between revisions)
| (12 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | <StructureSection load='2hix' size=' | + | <StructureSection load='2hix' size='350' side='right' scene='44/443730/Cv/2' caption='ATP-dependent DNA ligase complexed with ATP [[2hix]]'> |
| + | __TOC__ | ||
| + | == Function == | ||
| - | '''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 | + | '''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+. See also [[ATP-dependent DNA ligase from bacteriophage T7]].<br /> |
| + | * Mammalian '''LigD I''' ligates the nascent DNA of the lagging strand.<br /> | ||
| + | * '''LigD III''' complexes with XRCC1 in the process of nucleotide excision repair.<br /> | ||
| + | * '''LigD IV''' complexes with XRCC4 and catalyzes the last step in the non-homologous DNA end joining.<br /> | ||
| + | See more details in [[ATP-Dependent DNA Ligase (Bacteriophage T7)]]. | ||
==Disease== | ==Disease== | ||
| Line 9: | Line 15: | ||
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. | 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. | ||
| - | == | + | == Structural highlights == |
| - | + | Human LigD IV contains several domains: DNA-binding domain (residues 1-240); adenylation domain (residues 268-405) and the ca. 100 amino acid long BRCT motifs (residues 654-911). In the ATP-dependent LigD the ATP binds between 2 symmetry related LigD molecules. | |
| - | + | *<scene name='44/443730/Cv/4'>ATP binding site</scene> in ATP-dependent DNA ligase from ''S. solfataricus'' ([[2hix]]). <ref>PMID:17052461</ref> | |
| - | + | == 3D Structures of DNA ligase == | |
| + | [[DNA ligase 3D structures]] | ||
| - | **[[3p4h]], [[3ta5]], [[3ta7]] – LigD N-terminal – ''Candidatus korarchaeum cryptofilum''<br /> | ||
| - | **[[3gde]] – LigD – ''Archaeoglobus fulgidus''<br /> | ||
| - | **[[2hiv]] – SsLigD – ''Sulfolobus solfataricus''<br /> | ||
| - | **[[2hix]] - SsLigD + ATP<br /> | ||
| - | **[[2cfm]] - LigD + AMP – ''Pyrococcus furiosus''<br /> | ||
| - | **[[2fao]] - PaLigD polymerase domain – ''Pseudomonas aeruginosa''<br /> | ||
| - | **[[2faq]], [[2far]] - PaLigD polymerase domain + ATP + Mn<br /> | ||
| - | **[[1a0i]] – LigD + ATP – Bacteriophage T7<br /> | ||
| - | **[[4eq5]] – LigD + AMP – ''Thermococcus sibiricus'' | ||
| - | |||
| - | *NAD+-dependent LigD | ||
| - | |||
| - | **[[3jsl]], [[3jsn]] - LigD adenylation domain – ''Staphylococcus aureus''<br /> | ||
| - | **[[3ba8]], [[3ba9]], [[3baa]], [[3bab]], [[3bac]], [[4eeq]], [[4efb]], [[4efe]], [[4lh6]], [[4lh7]] - EfLigD adenylation domain + NMN + inhibitor – ''Enterococcus faecalis''<br /> | ||
| - | **[[1ta8]], [[1tae]] - EfLigD adenylation domain<br /> | ||
| - | **[[1zau]] - MtLigD adenylation domain – ''Mycobacterium tuberculosis''<br /> | ||
| - | **[[3sgi]] – MtLigD (mutant) + AMP<br /> | ||
| - | **[[1v9p]], [[1dgs]] – LigD – ''Thermos filiformis''<br /> | ||
| - | **[[1b04]] – LigD adenylation domain (mutant) – ''Geobacillus stearothermophilus''<br /> | ||
| - | **[[4glw]] – LigD A + NMN + inhibitor – ''Streptococcus pneumoniae''<br /> | ||
| - | **[[4glx]] – LigD + DNA + inhibitor - ''Escherichia coli''<br /> | ||
| - | |||
| - | *LigD | ||
| - | |||
| - | **[[2q2t]] – CvLigD + DNA + AMP + CMP – Chlorella virus<br /> | ||
| - | **[[2q2u]], [[ 1p8l]], [[ 1fvi]] - CvLigD + DNA + mononucleotide<br /> | ||
| - | **[[2owo]] – LigD + DNA + AMP + CMP – ''Escherichia coli''<br /> | ||
| - | **[[3qwu]] – LigD – ''Aquifex aeolicus''<br /> | ||
| - | **[[3pn1]] – HiLigD adenylation domain + inhibitor – ''Haemophilus influenzae''<br /> | ||
| - | **[[3uq8]] - HiLigD adenylation domain + NAD<br /> | ||
| - | **[[1l7b]] – LigD BRCT domain – ''Thermos thermophilus'' - NMR<br /> | ||
| - | **[[3rr5]] – LigD - ''Thermococcus'' | ||
| - | |||
| - | *Mammalian LigD I | ||
| - | |||
| - | **[[1x9n]] – hLigD I + DNA + AMP + CMP – human<br /> | ||
| - | **[[2od8]] – LigD I residues 32-53 + PCNA | ||
| - | |||
| - | *Mammalian LigD III | ||
| - | |||
| - | **[[3l2p]] – hLigD III residues 257-833 + DNA<br /> | ||
| - | **[[1uw0]] - hLigD III zinc-finger domain residues 1-117 – NMR<br /> | ||
| - | **[[1imo]], [[1in1]] - hLigD III BRCTdomain – NMR<br /> | ||
| - | **[[3pc7]] - hLigD III BRCTdomain<br /> | ||
| - | **[[3pc8]] - hLigD III BRCTdomain (mutant) + XRCC1<br /> | ||
| - | **[[3qvg]] - hLigD III BRCTdomain + XRCC1 | ||
| - | |||
| - | *Mammalian LigD IV | ||
| - | |||
| - | **[[3ii6]], [[ 1ik9]] – hLigD IV C-terminal BRCT domains + DNA repair protein XRCC4<br /> | ||
| - | **[[3w5o]] - hLigD IV <br /> | ||
| - | **[[2e2w]] - hLigD IV BRCT domain - NMR<br /> | ||
| - | **[[1z56]] – LigD IV + ligase interacting factor 1 - yeast<br /> | ||
| - | **[[3vnn]] - hLigD IV adenylation domain<br /> | ||
| - | **[[4hto]] - hLigD IV DNA-binding domain<br /> | ||
| - | **[[4htp]] - hLigD IV DNA-binding domain + artemis protein peptide<br /> | ||
| - | **[[3w1b]], [[3w1g]] - hLigD IV + artemis protein peptide<br /> | ||
| - | }} | ||
</StructureSection> | </StructureSection> | ||
| - | == | + | == References == |
| + | <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.''<br /> | ''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.''<br /> | ||
''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.'' | ''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.'' | ||
Current revision
| |||||||||||
References
- ↑ Pascal JM, Tsodikov OV, Hura GL, Song W, Cotner EA, Classen S, Tomkinson AE, Tainer JA, Ellenberger T. A flexible interface between DNA ligase and PCNA supports conformational switching and efficient ligation of DNA. Mol Cell. 2006 Oct 20;24(2):279-91. PMID:17052461 doi:10.1016/j.molcel.2006.08.015
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.
- Created with the participation of Audrey Kuan.
