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Molecular basis for DNA repair synthesis on short gaps by mycobacterial Primase-Polymerase C

DOI: 10.1038/s41467-020-18012-8 DOI Help

Authors: Nigel C. Brissett (University of Sussex) , Katerina Zabrady (University of Sussex) , Przemysław Płociński (University of Sussex; Institute of Medical Biology, Polish Academy of Sciences) , Julie Bianchi (Karolinska University Hospital; University of Sussex) , Małgorzata Korycka-Machała (Institute of Medical Biology, Polish Academy of Sciences) , Anna Brzostek (Institute of Medical Biology, Polish Academy of Sciences) , Jarosław Dziadek (Institute of Medical Biology, Polish Academy of Sciences) , Aidan J. Doherty (University of Sussex)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 11

State: Published (Approved)
Published: August 2020
Diamond Proposal Number(s): 14891

Open Access Open Access

Abstract: Cells 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.

Journal Keywords: Bacteria; DNA synthesis; Enzyme mechanisms; X-ray crystallography

Diamond Keywords: Bacteria; Enzymes

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography

Added On: 26/08/2020 10:19

Documents:
s41467-020-18012-8.pdf

Discipline Tags:

Life Sciences & Biotech Genetics Structural biology

Technical Tags:

Diffraction Macromolecular Crystallography (MX)