DNA ligase: Difference between revisions

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<StructureSection load='2hix' size='400' side='right' scene='DNA_ligase/Cv/1' caption='ATP-dependent DNA ligase complexed with ATP [[2hix]]'>
<StructureSection load='2hix' size='350' side='right' scene='44/443730/Cv/2' caption='ATP-dependent DNA ligase complexed with ATP [[2hix]]'>
__TOC__
== Function ==


[[Image:2hix.png|left|200px|thumb|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+.  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)]].


'''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.LigD contains several domains: adenylation domain; DNA-binding domain and the ca. 100 amino acid long BRCT motif.
{{TOC limit|limit=2}}
==Disease==
==Disease==
Known disease associated with this structure: DNA ligase I deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=126391 126391]]
Known disease associated with this structure: DNA ligase I deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=126391 126391]]
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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 ==  
== 3D Structures of DNA ligase ==
 
[[DNA ligase 3D structures]]
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
 
===ATP-dependent LigD===
 
[[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]] - EfLigD adenylation domain + 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''
 
===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 />
[[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


</StructureSection>
</StructureSection>


==REFERENCES==
== 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.''
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