Marques, C. A. , Tiengwe, C., Lemgruber Soares, L. , Damasceno, J. D., Scott, A., Paape, D. , Marcello, L. and McCulloch, R. (2016) Diverged composition and regulation of the Trypanosoma brucei origin recognition complex that mediates DNA replication initiation. Nucleic Acids Research, 44(10), pp. 4763-4784. (doi: 10.1093/nar/gkw147) (PMID:26951375) (PMCID:PMC4889932)
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Abstract
Initiation of DNA replication depends upon recognition of genomic sites, termed origins, by AAA+ ATPases. In prokaryotes a single factor binds each origin, whereas in eukaryotes this role is played by a six-protein origin recognition complex (ORC). Why eukaryotes evolved a multisubunit initiator, and the roles of each component, remains unclear. In Trypanosoma brucei, an ancient unicellular eukaryote, only one ORC-related initiator, TbORC1/CDC6, has been identified by sequence homology. Here we show that three TbORC1/CDC6-interacting factors also act in T. brucei nuclear DNA replication and demonstrate that TbORC1/CDC6 interacts in a high molecular complex in which a diverged Orc4 homologue and one replicative helicase subunit can also be found. Analysing the subcellular localization of four TbORC1/CDC6-interacting factors during the cell cycle reveals that one factor, TbORC1B, is not a static constituent of ORC but displays S-phase restricted nuclear localization and expression, suggesting it positively regulates replication. This work shows that ORC architecture and regulation are diverged features of DNA replication initiation in T. brucei, providing new insight into this key stage of eukaryotic genome copying.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Marcello, Dr Lucio and Paape, Dr Daniel and De Almeida Marques, Dr Catarina and Damasceno, Dr Jeziel and Scott, Mr Alan and Lemgruber Soares, Dr Leandro and McCulloch, Professor Richard |
| Authors: | Marques, C. A., Tiengwe, C., Lemgruber Soares, L., Damasceno, J. D., Scott, A., Paape, D., Marcello, L., and McCulloch, R. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine |
| Journal Name: | Nucleic Acids Research |
| Publisher: | Oxford University Press |
| ISSN: | 0305-1048 |
| ISSN (Online): | 1362-4962 |
| Published Online: | 06 March 2016 |
| Copyright Holders: | Copyright © 2016 The Authors |
| First Published: | First published in Nucleic Acids Research 44(10):4763-4784 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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