6btf | pdb_00006btf
DNA Polymerase Beta I260Q Ternary Complex
Structural highlights
FunctionDPOLB_HUMAN Repair polymerase that plays a key role in base-excision repair. Has 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity that removes the 5' sugar phosphate and also acts as a DNA polymerase that adds one nucleotide to the 3' end of the arising single-nucleotide gap. Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases.[1] [2] [3] [4] Publication Abstract from PubMedDNA polymerase beta (pol beta) fills single nucleotide gaps in DNA during base excision repair and non-homologous end-joining. Pol beta must select the correct nucleotide from among a pool of four nucleotides with similar structures and properties in order to maintain genomic stability during DNA repair. Here, we use a combination of X-ray crystallography, fluorescence resonance energy transfer and nuclear magnetic resonance to show that pol beta's ability to access the appropriate conformations both before and upon binding to nucleotide substrates is integral to its fidelity. Importantly, we also demonstrate that the inability of the I260Q mutator variant of pol beta to properly navigate this conformational landscape results in error-prone DNA synthesis. Our work reveals that precatalytic conformational rearrangements themselves are an important underlying mechanism of substrate selection by DNA pol beta. I260Q DNA polymerase beta highlights precatalytic conformational rearrangements critical for fidelity.,Liptak C, Mahmoud MM, Eckenroth BE, Moreno MV, East K, Alnajjar KS, Huang J, Towle-Weicksel JB, Doublie S, Loria JP, Sweasy JB Nucleic Acids Res. 2018 Sep 17. pii: 5098607. doi: 10.1093/nar/gky825. PMID:30239932[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
