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Evolution of complex clamp loaders
Author(s) -
Cann Isaac K.O.,
Chen YiHsing,
Lin Yuyen,
Kocherginskaya Svetlana A
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a513-b
Subject(s) - clamp , computer science , computer graphics (images) , clamping
Clamp loaders are the protein complexes essential for the switch from distributive DNA synthesis to processive DNA synthesis. Their invention in cells was therefore critical to the evolution of large genomes. In the eukaryotic lineage the clamp loader, also known as replication factor C (RFC), comprises a heteropentameric protein made up of four very similar small subunits and a large subunit. The striking similarities among the four RFC small subunits suggest that the four proteins evolved from a single ancestral gene. However, evidence for this hypothesis has been lacking. Interestingly, RFC homologs made up of a single small subunit and a large subunit were recently described in archaeal organisms. The RFC small subunit oligomerizes into a homotetramer to mimic the four small subunits in the eukaryotic RFC. The archaeal RFC small subunit proteins exhibit very high identities/similarities to the eukaryotic RFC small subunits and therefore may be similar to the ancestral protein in the archaeal/eukaryotic sister lineages. Recently, we discovered a novel RFC comprising two small subunits and a large subunit. The protein has been biochemically characterized together with its cognate clamp and DNA polymerases. Mutational analysis of this unique replication factor C, which appears to be the missing link in the evolution of complex clamp loaders as more complex organisms evolved, will be presented.