DNA ligase

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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]]'>
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[[Image:2hix.png|left|200px|thumb|Crystal Structure of DNA ligase [[2hix]]]]
[[Image:2hix.png|left|200px|thumb|Crystal Structure of DNA ligase [[2hix]]]]
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{{STRUCTURE_2hix| PDB=2hix | SIZE=400| SCENE=DNA_ligase/Cv/1 |right|CAPTION=ATP-dependent DNA ligase complexed with ATP [[2hix]] }}
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'''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.
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'''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+. Mamlian 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.
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==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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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.<br />
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.<br />
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[[2e2w]] - hLigD IV BRCT domain - NMR
[[2e2w]] - hLigD IV BRCT domain - NMR
[[1z56]] – LigD IV + ligase interacting factor 1 - yeast
[[1z56]] – LigD IV + ligase interacting factor 1 - yeast
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</StructureSection>
==REFERENCES==
==REFERENCES==

Revision as of 12:38, 7 June 2012

ATP-dependent DNA ligase complexed with ATP 2hix

Drag the structure with the mouse to rotate

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.
Created with the participation of Audrey Kuan.

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