Targeting of human DNA polymerase ι to the replication machinery via interaction with PCNA

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

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Abstract

Human DNA polymerase ι(hPolι) promotes translesion synthesis by inserting nucleotides opposite highly distorting or noninstructional DNA lesions. Here, we provide evidence for the physical interaction of hPolι with proliferating cell nuclear antigen (PCNA), and show that PCNA, together with replication factor C (RFC) and replication protein A (RPA), stimulates the DNA synthetic activity of hPolι. In the presence of these protein factors, on undamaged DNA, the efficiency (Vmax/Km) of correct nucleotide incorporation by hPoι is increased ≈80-150-fold, and this increase in efficiency results from a reduction in the apparent Km, for the nucleotide. PCNA, RFC, and RPA also stimulate nucleotide incorporation opposite the 3′-T of the (6-4) thymine-thymine (T-T) photoproduct and opposite an abasic site. The interaction of hPolι with PCNA implies that the targeting of this polymerase to the replication machinery stalled at a lesion site is achieved via this association.

Original languageEnglish
Pages (from-to)14256-14261
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number25
DOIs
Publication statusPublished - Dec 4 2001

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