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Ternary complex of Prim-PolC from Mycobacterium smegmatis with 2nt gapped DNA and UpNHppTernary complex of Prim-PolC from Mycobacterium smegmatis with 2nt gapped DNA and UpNHpp
Structural highlights
FunctionPublication Abstract from PubMedCells utilise specialized polymerases from the Primase-Polymerase (Prim-Pol) superfamily to maintain genome stability. Prim-Pol's function in genome maintenance pathways including replication, repair and damage tolerance. Mycobacteria contain multiple Prim-Pols required for lesion repair, including Prim-PolC that performs short gap repair synthesis during excision repair. To understand the molecular basis of Prim-PolC's gap recognition and synthesis activities, we elucidated crystal structures of pre- and post-catalytic complexes bound to gapped DNA substrates. These intermediates explain its binding preference for short gaps and reveal a distinctive modus operandi called Synthesis-dependent Template Displacement (STD). This mechanism enables Prim-PolC to couple primer extension with template base dislocation, ensuring that the unpaired templating bases in the gap are ushered into the active site in an ordered manner. Insights provided by these structures establishes the molecular basis of Prim-PolC's gap recognition and extension activities, while also illuminating the mechanisms of primer extension utilised by closely related Prim-Pols. Molecular basis for DNA repair synthesis on short gaps by mycobacterial Primase-Polymerase C.,Brissett NC, Zabrady K, Plocinski P, Bianchi J, Korycka-Machala M, Brzostek A, Dziadek J, Doherty AJ Nat Commun. 2020 Aug 21;11(1):4196. doi: 10.1038/s41467-020-18012-8. PMID:32826907[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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