5iij | pdb_00005iij
Crystal structure of the pre-catalytic ternary complex of DNA polymerase lambda with a templating 8-oxo-dG and an incoming dCTP
Structural highlights
FunctionDPOLL_HUMAN Repair polymerase. Involved in base excision repair (BER) responsible for repair of lesions that give rise to abasic (AP) sites in DNA. Has both DNA polymerase and terminal transferase activities. Has a 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity.[1] [2] Publication Abstract from PubMed8-oxo-7,8-dihydroxy-2'-deoxyguanosine (8-oxo-dG) has high mutagenic potential as it is prone to mispair with deoxyadenine (dA). In order to maintain genomic integrity, post-replicative 8-oxo-dG:dA mispairs are removed through DNA polymerase lambda (Pol lambda)-dependent MUTYH-initiated base excision repair (BER). Here, we describe seven novel crystal structures and kinetic data that fully characterize 8-oxo-dG bypass by Pol lambda. We demonstrate that Pol lambda has a flexible active site that can tolerate 8-oxo-dG in either the anti- or syn-conformation. Importantly, we show that discrimination against the pro-mutagenic syn-conformation occurs at the extension step and identify the residue responsible for this selectivity. This residue acts as a kinetic switch, shunting repair toward long-patch BER upon correct dCMP incorporation, thus enhancing repair efficiency. Moreover, this switch also provides a potential mechanism to increase repair fidelity of MUTYH-initiated BER. A fidelity mechanism in DNA polymerase lambda promotes error-free bypass of 8-oxo-dG.,Burak MJ, Guja KE, Hambardjieva E, Derkunt B, Garcia-Diaz M EMBO J. 2016 Aug 1. pii: e201694332. PMID:27481934[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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