4RU9

Crystal structure of human DNA polymerase eta inserting dCMPNPP opposite a MeFapy-dG adducted DNA template

Summary for 4RU9

• Entry DOI: 10.2210/pdb4ru9/pdb
• Related: 4RUA
• Descriptor: DNA polymerase eta, Nucleic acids Template: CAT(MF7)ATGACGCT, Nucleic acids Primar: AGCGTCAT, ... (6 entities in total)
• Functional Keywords: dna damage, dna-directed dna polymerase, cytidine triphosphate, y-family polymerase, trans-lesion synthesis (tls), dna binding, mefapy-dg lesion bypass, 2, 6-diamino-4-hydroxy-n(5)-(methyl)-formamidopyrimidine (mefapy-dg) lesion, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : Q9Y253
• Total number of polymer chains: 3
• Total formula weight: 54961.24

Authors

Patra, A.,Egli, M. (deposition date: 2014-11-18, release date: 2015-08-05, Last modification date: 2023-09-20)

Primary citation

Patra, A.,Banerjee, S.,Johnson Salyard, T.L.,Malik, C.K.,Christov, P.P.,Rizzo, C.J.,Stone, M.P.,Egli, M.
Structural Basis for Error-Free Bypass of the 5-N-Methylformamidopyrimidine-dG Lesion by Human DNA Polymerase eta and Sulfolobus solfataricus P2 Polymerase IV.
J.Am.Chem.Soc., 137:7011-7014, 2015

PubMed Abstract: N(6)-(2-Deoxy-D-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5-N-methylformamidopyrimidine (MeFapy-dG) arises from N7-methylation of deoxyguanosine followed by imidazole ring opening. The lesion has been reported to persist in animal tissues. Previous in vitro replication bypass investigations of the MeFapy-dG adduct revealed predominant insertion of C opposite the lesion, dependent on the identity of the DNA polymerase (Pol) and the local sequence context. Here we report crystal structures of ternary Pol·DNA·dNTP complexes between MeFapy-dG-adducted DNA template:primer duplexes and the Y-family polymerases human Pol η and P2 Pol IV (Dpo4) from Sulfolobus solfataricus. The structures of the hPol η and Dpo4 complexes at the insertion and extension stages, respectively, are representative of error-free replication, with MeFapy-dG in the anti conformation and forming Watson-Crick pairs with dCTP or dC.

PubMed: 25988947
DOI: 10.1021/jacs.5b02701

Experimental method

X-RAY DIFFRACTION (2.65 Å)