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Molecular and Cellular Biology, November 2001, p. 7199-7206, Vol. 21, No. 21
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.21.7199-7206.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Physical and Functional Interactions of Human DNA Polymerase eta  with PCNA

Lajos Haracska,1 Robert E. Johnson,1 Ildiko Unk,1 Barbara Phillips,2 Jerard Hurwitz,2 Louise Prakash,1 and Satya Prakash1,*

Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, Texas 77555-1061,1 and Department of Molecular Biology and Virology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021-60072

Received 5 July 2001/Returned for modification 20 July 2001/Accepted 27 July 2001

Human DNA polymerase eta  (hPoleta ) functions in the error-free replication of UV-damaged DNA, and mutations in hPoleta cause cancer-prone syndrome, the variant form of xeroderma pigmentosum. However, in spite of its key role in promoting replication through a variety of distorting DNA lesions, the manner by which hPoleta is targeted to the replication machinery stalled at a lesion site remains unknown. Here, we provide evidence for the physical interaction of hPoleta with proliferating cell nuclear antigen (PCNA) and show that mutations in the PCNA binding motif of hPoleta inactivate this interaction. PCNA, together with replication factor C and replication protein A, stimulates the DNA synthetic activity of hPoleta , and steady-state kinetic studies indicate that this stimulation accrues from an increase in the efficiency of nucleotide insertion resulting from a reduction in the apparent Km for the incoming nucleotide.

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

Molecular and Cellular Biology, November 2001, p. 7199-7206, Vol. 21, No. 21
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.21.7199-7206.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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