5T14

DNA polymerase kappa extending beyond a bulky major benzo[a]pyrene adduct

Summary for 5T14

• Entry DOI: 10.2210/pdb5t14/pdb
• Related: 4U6P 4U7C
• Descriptor: DNA polymerase kappa, DNA, MAGNESIUM ION, ... (7 entities in total)
• Functional Keywords: dna repair dna replication benzopyrene ternary complex, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 135883.08

Authors

Jha, V.K.,Ling, H. (deposition date: 2016-08-17, release date: 2016-12-21, Last modification date: 2024-03-06)

Primary citation

Jha, V.,Ling, H.
Structural basis of accurate replication beyond a bulky major benzo[a]pyrene adduct by human DNA polymerase kappa.
DNA Repair (Amst.), 49:43-50, 2017

PubMed Abstract: Human Y-family DNA polymerase kappa (polκ) is specialized to bypass bulky lesions in DNA in an error-free way, thus protecting cells from carcinogenic bulky DNA adducts. Benzo[a]pyrene (BP) is one of the most ubiquitous polycyclic aromatic hydrocarbons and an environmental carcinogen. BP covalently modifies DNA and generates mutagenic, bulky adducts. The major BP adduct formed in cells is 10S (+)-trans-anti-BP-N-dG adduct (BP-dG), which is associated with cancer. The molecular mechanism of how polκ replicates BP-dG accurately is not clear. Here we report the structure of polκ captured at the lesion-extension stage: the enzyme is extending the primer strand after the base pair containing the BP-dG adduct in the template strand at the -1 position. Polκ accommodates the BP adduct in the nascent DNA's minor groove and keeps the adducted DNA helix in a B-form. Two water molecules cover the edge of the minor groove of the replicating base pair (0 position), which is secured by the BP ring in the -1 position in a 5' orientation. The 5' oriented BP adduct keeps correct Watson-Crick base pairing in the active site and promotes high fidelity replication. Our structural and biochemical data reveal a unique molecular basis for accurate DNA replication right after the bulky lesion BP-dG.

PubMed: 27894903
DOI: 10.1016/j.dnarep.2016.11.001

Experimental method

X-RAY DIFFRACTION (3 Å)