3SI8

Human DNA polymerase eta - DNA ternary complex with the 5'T of a CPD in the active site (TT2)

Replaces:  3MR4

Summary for 3SI8

• Entry DOI: 10.2210/pdb3si8/pdb
• Related: 3MR2 3MR3 3MR5 3MR6
• Descriptor: DNA polymerase eta, COBALT (II) ION, DNA (5'-D(*TP*A*AP*CP*(TTD)P*AP*TP*GP*AP*CP*GP*C)-3'), ... (11 entities in total)
• Functional Keywords: protein-dna complex, multiple domains, three are alpha/beta fold and one of the four is helical fold, dna polymerase, dna binding, mg2+ and dntp binding, affinity tag is added and partially removed at the n-terminal end, nucleus, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q9Y253
• Total number of polymer chains: 3
• Total formula weight: 57503.69

Authors

Biertumpfel, C.,Zhao, Y.,Kondo, Y.,Ramon-Maiques, S.,Gregory, M.,Lee, J.Y.,Masutani, C.,Lehmann, A.R.,Hanaoka, F.,Yang, W. (deposition date: 2011-06-17, release date: 2011-08-03, Last modification date: 2024-03-13)

Primary citation

Biertumpfel, C.,Zhao, Y.,Kondo, Y.,Ramon-Maiques, S.,Gregory, M.,Lee, J.Y.,Masutani, C.,Lehmann, A.R.,Hanaoka, F.,Yang, W.
Structure and mechanism of human DNA polymerase eta.
Nature, 465:1044-1048, 2010

PubMed Abstract: The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Poleta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Poleta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Poleta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Poleta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Poleta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Poleta in replicating through D loop and DNA fragile sites.

PubMed: 20577208
DOI: 10.1038/nature09196

Experimental method

X-RAY DIFFRACTION (2.15 Å)