3MFI

DNA Polymerase Eta in Complex With a cis-syn Thymidine Dimer

Summary for 3MFI

• Entry DOI: 10.2210/pdb3mfi/pdb
• Related: 1JIH 3MFH
• Descriptor: DNA polymerase eta, 5'-D(*GP*TP*CP*CP*TP*CP*CP*CP*CP*TP*(DOC))-3', 5'-D(*TP*AP*AP*(TTD)P*GP*AP*GP*GP*GP*GP*AP*GP*GP*AP*C)-3', ... (7 entities in total)
• Functional Keywords: dna damage, dna repair, dna replication, dna synthesis, nucleus, dna-binding, magnesium, metal-binding, dna-directed dna polymerase, mutator protein, nucleotidyltransferase, dna polymerase eta, protein-dna complex, thymidine dimer, cpd, uv-damage, transferase-dna complex, transferase/dna
• Biological source: Saccharomyces cerevisiae (yeast); More
• Cellular location: Nucleus : Q04049
• Total number of polymer chains: 3
• Total formula weight: 67777.70

Authors

Silverstein, T.D.,Johnson, R.E.,Jain, R.,Prakash, L.,Prakash, S.,Aggarwal, A.K. (deposition date: 2010-04-02, release date: 2010-06-23, Last modification date: 2023-09-06)

Primary citation

Silverstein, T.D.,Johnson, R.E.,Jain, R.,Prakash, L.,Prakash, S.,Aggarwal, A.K.
Structural basis for the suppression of skin cancers by DNA polymerase eta.
Nature, 465:1039-1043, 2010

PubMed Abstract: DNA polymerase eta (Poleta) is unique among eukaryotic polymerases in its proficient ability for error-free replication through ultraviolet-induced cyclobutane pyrimidine dimers, and inactivation of Poleta (also known as POLH) in humans causes the variant form of xeroderma pigmentosum (XPV). We present the crystal structures of Saccharomyces cerevisiae Poleta (also known as RAD30) in ternary complex with a cis-syn thymine-thymine (T-T) dimer and with undamaged DNA. The structures reveal that the ability of Poleta to replicate efficiently through the ultraviolet-induced lesion derives from a simple and yet elegant mechanism, wherein the two Ts of the T-T dimer are accommodated in an active site cleft that is much more open than in other polymerases. We also show by structural, biochemical and genetic analysis that the two Ts are maintained in a stable configuration in the active site via interactions with Gln 55, Arg 73 and Met 74. Together, these features define the basis for Poleta's action on ultraviolet-damaged DNA that is crucial in suppressing the mutagenic and carcinogenic consequences of sun exposure, thereby reducing the incidence of skin cancers in humans.

PubMed: 20577207
DOI: 10.1038/nature09104

Experimental method

X-RAY DIFFRACTION (1.76 Å)