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Molecular and Cellular Biology, February 2002, p. 784-791, Vol. 22, No. 3
0270-7306/01/$04.00+0     DOI: 10.1128/MCB.22.3.784-791.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Stimulation of DNA Synthesis Activity of Human DNA Polymerase {kappa} by PCNA

Lajos Haracska, Ildiko Unk, Robert E. Johnson, Barbara B. Phillips, Jerard Hurwitz, Louise Prakash, and Satya Prakash*

Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, Texas 77555-1061

Received 20 September 2001/ Returned for modification 19 October 2001/ Accepted 23 October 2001

Humans have three DNA polymerases, Pol{eta}, Pol{kappa}, and Pol{iota}, which are able to promote replication through DNA lesions. However, the mechanism by which these DNA polymerases are targeted to the replication machinery stalled at a lesion site has remained unknown. Here, we provide evidence for the physical interaction of human Pol{kappa} (hPol{kappa}) with proliferating cell nuclear antigen (PCNA) and show that PCNA, replication factor C (RFC), and replication protein A (RPA) act cooperatively to stimulate the DNA synthesis activity of hPol{kappa}. The processivity of hPol{kappa}, however, is not significantly increased in the presence of these protein factors. The efficiency (Vmax/Km) of correct nucleotide incorporation by hPol{kappa} is enhanced ~50- to 200-fold in the presence of PCNA, RFC, and RPA, and this increase in efficiency is achieved by a reduction in the apparent Km for the nucleotide. Although in the presence of these protein factors, the efficiency of the insertion of an A nucleotide opposite an abasic site is increased ~40-fold, this reaction still remains quite inefficient; thus, it is unlikely that hPol{kappa} would bypass an abasic site by inserting a nucleotide opposite the site.

* Corresponding author. Mailing address: Sealy Center for Molecular Science, University of Texas Medical Branch, 6.104 Blocker Medical Research Building, 11th and Mechanic St., Galveston, TX 77555-1061. Phone: (409) 747-8602. Fax: (409) 747-8608. E-mail: sprakash{at}scms.utmb.edu.

Molecular and Cellular Biology, February 2002, p. 784-791, Vol. 22, No. 3
0022-538X/01/$04.00+0     DOI: 10.1128/MCB.22.3.784-791.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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