%0 Journal Article
%T Clamp loader ATPases and the evolution of DNA replication machinery
%A Brian A Kelch
%A Debora L Makino
%A Mike O'Donnell
%A John Kuriyan
%J BMC Biology
%D 2012
%I BioMed Central
%R 10.1186/1741-7007-10-34
%X High-speed replication of chromosomal DNA requires the DNA polymerase to be attached to a sliding clamp (known as proliferating cell nuclear antigen, or PCNA, in eukaryotes) that prevents the polymerase from falling off DNA [1,2]. In all cells and in some viruses, the clamp is a ring-shaped protein complex that encircles DNA, forming a sliding platform on which DNA polymerases and other proteins that move along DNA are assembled. Sliding clamps play a part in DNA replication, DNA repair, cell cycle control and modification of chromatin structure [3,4], and defects in several clamp-associated factors are associated with cancer and other disorders caused by abnormalities in DNA replication and repair [5].Because sliding clamps encircle DNA but do not interact tightly with it, they can slide along the double helix by diffusion [6-9]. Sliding clamps from different branches of life have different subunit stoichiometry (they are dimers in bacteria [10] and trimers in eukarya, archaea and bacteriophage [11-15]) and their sequences have diverged beyond recognition. Nevertheless, their structures are remarkably similar. The conserved structure is an elegant symmetrical elaboration of a simple ¦Â-¦Á-¦Â motif, repeated 12 times around a circle [10,14]. The circular geometry is broken when the clamp is opened for loading onto DNA, but the elegance is retained during the loading step as the clamp assumes a helical symmetry that reflects the helical symmetry of DNA (see below).The increase in the processivity and speed of DNA synthesis when DNA polymerases are engaged to sliding clamps is very considerable. For example, in the absence of the clamp, the polymerase subunit of the bacterial replicase synthesizes DNA at a rate of about 10 base pairs per second [16] and is hardly processive. In contrast, the same polymerase subunit synthesizes 500 to 1,000 nucleotides per second when bound to the sliding clamp [17-19]. To consider a startling analogy based on scaling linear dimensions, i
%U http://www.biomedcentral.com/1741-7007/10/34