1ryr
From Proteopedia
(New page: 200px<br /><applet load="1ryr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ryr, resolution 2.28Å" /> '''REPLICATION OF A CIS...) |
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| - | [[Image:1ryr.gif|left|200px]]<br /><applet load="1ryr" size=" | + | [[Image:1ryr.gif|left|200px]]<br /><applet load="1ryr" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ryr, resolution 2.28Å" /> | caption="1ryr, resolution 2.28Å" /> | ||
'''REPLICATION OF A CIS-SYN THYMINE DIMER AT ATOMIC RESOLUTION'''<br /> | '''REPLICATION OF A CIS-SYN THYMINE DIMER AT ATOMIC RESOLUTION'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Ultraviolet light damages DNA by catalysing covalent bond formation | + | Ultraviolet light damages DNA by catalysing covalent bond formation between adjacent pyrimidines, generating cis-syn cyclobutane pyrimidine dimers (CPDs) as the most common lesion. CPDs block DNA replication by high-fidelity DNA polymerases, but they can be efficiently bypassed by the Y-family DNA polymerase pol eta. Mutations in POLH encoding pol eta are implicated in nearly 20% of xeroderma pigmentosum, a human disease characterized by extreme sensitivity to sunlight and predisposition to skin cancer. Here we have determined two crystal structures of Dpo4, an archaeal pol eta homologue, complexed with CPD-containing DNA, where the 3' and 5' thymine of the CPD separately serves as a templating base. The 3' thymine of the CPD forms a Watson-Crick base pair with the incoming dideoxyATP, but the 5' thymine forms a Hoogsteen base pair with the dideoxyATP in syn conformation. Dpo4 retains a similar tertiary structure, but each unusual DNA structure is individually fitted into the active site for catalysis. A model of the pol eta-CPD complex built from the crystal structures of Saccharomyces cerevisiae apo-pol eta and the Dpo4-CPD complex suggests unique features that allow pol eta to efficiently bypass CPDs. |
==About this Structure== | ==About this Structure== | ||
| - | 1RYR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sulfolobus_solfataricus Sulfolobus solfataricus] with CA and ATP as [http://en.wikipedia.org/wiki/ligands ligands]. This structure | + | 1RYR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sulfolobus_solfataricus Sulfolobus solfataricus] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=ATP:'>ATP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1PM0. Active as [http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RYR OCA]. |
==Reference== | ==Reference== | ||
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[[Category: tt-dimer]] | [[Category: tt-dimer]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:56:03 2008'' |
Revision as of 12:56, 21 February 2008
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REPLICATION OF A CIS-SYN THYMINE DIMER AT ATOMIC RESOLUTION
Overview
Ultraviolet light damages DNA by catalysing covalent bond formation between adjacent pyrimidines, generating cis-syn cyclobutane pyrimidine dimers (CPDs) as the most common lesion. CPDs block DNA replication by high-fidelity DNA polymerases, but they can be efficiently bypassed by the Y-family DNA polymerase pol eta. Mutations in POLH encoding pol eta are implicated in nearly 20% of xeroderma pigmentosum, a human disease characterized by extreme sensitivity to sunlight and predisposition to skin cancer. Here we have determined two crystal structures of Dpo4, an archaeal pol eta homologue, complexed with CPD-containing DNA, where the 3' and 5' thymine of the CPD separately serves as a templating base. The 3' thymine of the CPD forms a Watson-Crick base pair with the incoming dideoxyATP, but the 5' thymine forms a Hoogsteen base pair with the dideoxyATP in syn conformation. Dpo4 retains a similar tertiary structure, but each unusual DNA structure is individually fitted into the active site for catalysis. A model of the pol eta-CPD complex built from the crystal structures of Saccharomyces cerevisiae apo-pol eta and the Dpo4-CPD complex suggests unique features that allow pol eta to efficiently bypass CPDs.
About this Structure
1RYR is a Single protein structure of sequence from Sulfolobus solfataricus with and as ligands. This structure supersedes the now removed PDB entry 1PM0. Active as DNA-directed DNA polymerase, with EC number 2.7.7.7 Full crystallographic information is available from OCA.
Reference
Replication of a cis-syn thymine dimer at atomic resolution., Ling H, Boudsocq F, Plosky BS, Woodgate R, Yang W, Nature. 2003 Aug 28;424(6952):1083-7. Epub 2003 Aug 6. PMID:12904819
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