title: A proposal: Evolution of PCNA's role as a marker of newly replicated DNA.
abstract: Processivity clamps that hold DNA polymerases to DNA for processivity were the first proteins known to encircle the DNA duplex. At the time, polymerase processivity was thought to be the only function of ring shaped processivity clamps. But studies from many laboratories have identified numerous proteins that bind and function with sliding clamps. Among these processes are mismatch repair and nucleosome assembly. Interestingly, there exist polymerases that are highly processive and do not require clamps. Hence, DNA polymerase processivity does not intrinsically require that sliding clamps evolved for this purpose. We propose that polymerases evolved to require clamps as a way of ensuring that clamps are deposited on newly replicated DNA. These clamps are then used on the newly replicated daughter strands, for processes important to genomic integrity, such as mismatch repair and the assembly of nucleosomes to maintain epigenetic states of replicating cells during development.
authors.affiliation: Rockefeller University and HHMI, 1230 York Avenue, Box 228, New York, NY 10065, United States.
authors.forename: Roxana
authors.initials: R
authors.lastname: Georgescu
authors.affiliation: Rockefeller University and HHMI, 1230 York Avenue, Box 228, New York, NY 10065, United States.
authors.forename: Lance
authors.initials: L
authors.lastname: Langston
authors.affiliation: Rockefeller University and HHMI, 1230 York Avenue, Box 228, New York, NY 10065, United States. Electronic address: odonnel@rockefeller.edu.
authors.forename: Mike
authors.initials: M
authors.lastname: O'Donnell
mesh_terms: D001419:Bacteria / Q000235:genetics; D004247:DNA / Q000378:metabolism; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D056890:Eukaryota / Q000235:genetics; D019143:Evolution, Molecular; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism*
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D004247:DNA; D004259:DNA-Directed DNA Polymerase
keywords: DNA replication; PCNA; β-Clamp