A single domain in human DNA polymerase ι mediates interaction with PCNA

Implications for translesion DNA synthesis

Lajos Haracska, Narottam Acharya, Ildiko Unk, Robert E. Johnson, Jerard Hurwitz, Louise Prakash, Satya Prakash

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

DNA polymerases (Pols) of the Y family rescue stalled replication forks by promoting replication through DNA lesions. Humans have four Y family Pols, η, ι, κ, and Rev1, of which Pols η, ι, and κ have been shown to physically interact with proliferating cell nuclear antigen (PCNA) and be functionally stimulated by it. However, in sharp contrast to the large increase in processivity that PCNA binding imparts to the replicative Pol, Polδ, the processivity of Y family Pols is not enhanced upon PCNA binding. Instead, PCNA binding improves the efficiency of nucleotide incorporation via a reduction in the apparent Km for the nucleotide. Here we show that Polι interacts with PCNA via only one of its conserved PCNA binding motifs, regardless of whether PCNA is bound to DNA or not. The mode of PCNA binding by Polι is quite unlike that in Polδ, where multisite interactions with PCNA provide for a very tight binding of the replicating Pol with PCNA. We discuss the implications of these observations for the accuracy of DNA synthesis during translesion synthesis and for the process of Pol exchange at the lesion site.

Original languageEnglish (US)
Pages (from-to)1183-1190
Number of pages8
JournalMolecular and Cellular Biology
Volume25
Issue number3
DOIs
StatePublished - Feb 2005

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Proliferating Cell Nuclear Antigen
DNA-Directed DNA Polymerase
DNA
Nucleotides
DNA Replication

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

A single domain in human DNA polymerase ι mediates interaction with PCNA : Implications for translesion DNA synthesis. / Haracska, Lajos; Acharya, Narottam; Unk, Ildiko; Johnson, Robert E.; Hurwitz, Jerard; Prakash, Louise; Prakash, Satya.

In: Molecular and Cellular Biology, Vol. 25, No. 3, 02.2005, p. 1183-1190.

Research output: Contribution to journalArticle

Haracska, Lajos ; Acharya, Narottam ; Unk, Ildiko ; Johnson, Robert E. ; Hurwitz, Jerard ; Prakash, Louise ; Prakash, Satya. / A single domain in human DNA polymerase ι mediates interaction with PCNA : Implications for translesion DNA synthesis. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 3. pp. 1183-1190.
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