1rys: Difference between revisions
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'''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== | ||
1RYS 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, NA, ATP and EDO as [http://en.wikipedia.org/wiki/ligands ligands]. This structure | 1RYS 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>, <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=ATP:'>ATP</scene> and <scene name='pdbligand=EDO:'>EDO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1PM8. The following page contains interesting information on the relation of 1RYS with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb91_1.html Thymine Dimers]]. 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=1RYS OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: polymerase]] | [[Category: polymerase]] | ||
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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
1RYS is a Single protein structure of sequence from Sulfolobus solfataricus with CA, NA, ATP and EDO as ligands. This structure supersedes the now removed PDB entry 1PM8. The following page contains interesting information on the relation of 1RYS with [Thymine Dimers]. 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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