Physical and functional interactions of human DNA polymerase η with PCNA

L. Haracska, R. E. Johnson, I. Unk, B. Phillips, J. Hurwitz, Louise Prakash, Satya Prakash

Research output: Contribution to journalArticle

193 Citations (Scopus)

Abstract

Human DNA polymerase η (hPolη) functions in the error-free replication of UV-damaged DNA, and mutations in hPolη 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 hPolη is targeted to the replication machinery stalled at a lesion site remains unknown. Here, we provide evidence for the physical interaction of hPolη with proliferating cell nuclear antigen (PCNA) and show that mutations in the PCNA binding motif of hPolη inactivate this interaction. PCNA, together with replication factor C and replication protein A, stimulates the DNA synthetic activity of hPolη, 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.

Original languageEnglish (US)
Pages (from-to)7199-7206
Number of pages8
JournalMolecular and Cellular Biology
Volume21
Issue number21
DOIs
StatePublished - 2001

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Proliferating Cell Nuclear Antigen
DNA-Directed DNA Polymerase
DNA
Nucleotides
Replication Protein C
Replication Protein A
Mutation
Human Activities
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Physical and functional interactions of human DNA polymerase η with PCNA. / Haracska, L.; Johnson, R. E.; Unk, I.; Phillips, B.; Hurwitz, J.; Prakash, Louise; Prakash, Satya.

In: Molecular and Cellular Biology, Vol. 21, No. 21, 2001, p. 7199-7206.

Research output: Contribution to journalArticle

Haracska, L. ; Johnson, R. E. ; Unk, I. ; Phillips, B. ; Hurwitz, J. ; Prakash, Louise ; Prakash, Satya. / Physical and functional interactions of human DNA polymerase η with PCNA. In: Molecular and Cellular Biology. 2001 ; Vol. 21, No. 21. pp. 7199-7206.
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