The crystal structure of an unusual processivity factor, herpes simplex virus UL42, bound to the C terminus of its cognate polymerase

Herpes simplex virus DNA polymerase is a heterodimer composed of a catalyti c subunit, Pol, and an unusual processivity subunit, UL42, which, unlike pr ocessivity factors such as PCNA, directly binds DNA. The crystal structure of a complex of the C-terminal 36 residues of Pot bound to residues 1-319 o f UL42 reveals remarkable similarities between UL42 and PCNA despite contra sting biochemical properties and lack of sequence homology. Moreover, the P ol-UL42 interaction resembles the interaction between the cell cycle regula tor p21 and PCNA. The structure and previous data suggest that the UL42 mon omer interacts with DNA quite differently than does multimeric toroidal PCN A, The details of the structure lead to a model for the mechanism of UL42, provide the basis for drug design, and allow modeling of other proteins tha t lack sequence homology with UL42 or PCNA.