The human CTF4-orthologue AND-1 interacts with DNA polymerase α/primase via its unique C-terminal HMG box
The Royal Society
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Pellegrini, L., Kilkenny, M., Simon, A., Mainwaring, J., Wirthensohn, D., & Holzer, S. (2017). The human CTF4-orthologue AND-1 interacts with DNA polymerase α/primase via its unique C-terminal HMG box. Open Biology https://doi.org/10.1098/rsob.170217
A dynamic multi-protein assembly known as the replisome is responsible for DNA synthesis in eukaryotic cells. In yeast, the hub protein Ctf4 bridges DNA helicase and DNA polymerase and recruits factors with roles in metabolic processes coupled to DNA replication. An important question in DNA replication is the extent to which the molecular architecture of the replisome is conserved between yeast and higher eukaryotes. Here we describe the biochemical basis for the interaction of the human CTF4-orthologue AND-1 with Pol α/primase, the replicative polymerase that initiates DNA synthesis. AND-1 has maintained the trimeric structure of yeast Ctf4, driven by its conserved SepB domain. However, the primary interaction of AND-1 with Pol α/primase is mediated by its C-terminal HMG box, unique to mammalian AND-1, which binds the B subunit, at the same site targeted by the SV40 T antigen for viral replication. In addition, we report a novel DNA-binding activity in AND-1, which might promote the correct positioning of Pol α/primase on the lagging-strand template at the replication fork. Our findings provide a biochemical basis for the specific interaction between two critical components of the human replisome, and indicate that important principles of replisome architecture have changed significantly in evolution.
DNA replication, replisome, protein–protein interactions, protein–DNA interactions, DNA polymerase, protein hub
This work was supported by a Wellcome Trust investigator award to L.P. (104641/Z/14/Z), a Cambridge Gates PhD scholarship to A.C.S., a PhD fellowship of the Boehringer-Ingelheim Fonds and awards from the Janggen-Pöhn-Stiftung and the Swiss National Science Foundation to S.H.
WELLCOME TRUST (104641/Z/14/Z)
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External DOI: https://doi.org/10.1098/rsob.170217
This record's URL: https://www.repository.cam.ac.uk/handle/1810/273551
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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