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

Brissett, Nigel C, Zabrady, Katerina, Płociński, Przemysław, Bianchi, Julie, Korycka-Machała, Małgorzata, Brzostek, Anna, Dziadek, Jarosław and Doherty, Aidan J (2020) Molecular basis for DNA repair synthesis on short gaps by mycobacterial Primase-Polymerase C. Nature Communications, 11. a4196. ISSN 2041-1723

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 25 Aug 2020 06:50
Last Modified: 25 Aug 2020 07:01
URI: http://sro.sussex.ac.uk/id/eprint/93259

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