Physical and Functional Interactions of Human DNA Polymerase Eta with PCNA

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2001 Oct 5

PMID 11585903

Citations 108

Authors

L Haracska

R E Johnson

I Unk

B Phillips

J Hurwitz

L Prakash

S Prakash

Affiliations

Soon will be listed here.

Abstract

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 K(m) for the incoming nucleotide.

Citing Articles

Proliferating cell nuclear antigen inhibitors block distinct stages of herpes simplex virus infection.

Packard J, Williams M, Fromuth D, Dembowski J PLoS Pathog. 2023; 19(7):e1011539.

PMID: 37486931 PMC: 10399828. DOI: 10.1371/journal.ppat.1011539.

Post-Translational Modifications of PCNA: Guiding for the Best DNA Damage Tolerance Choice.

Belli G, Colomina N, Castells-Roca L, Lorite N J Fungi (Basel). 2022; 8(6).

PMID: 35736104 PMC: 9225081. DOI: 10.3390/jof8060621.

The inner side of yeast PCNA contributes to genome stability by mediating interactions with Rad18 and the replicative DNA polymerase δ.

Toth R, Halmai M, Gyorfy Z, Balint E, Unk I Sci Rep. 2022; 12(1):5163.

PMID: 35338218 PMC: 8956578. DOI: 10.1038/s41598-022-09208-7.

The ubiquitin-binding domain of DNA polymerase η directly binds to DNA clamp PCNA and regulates translesion DNA synthesis.

Manohar K, Khandagale P, Patel S, Sahu J, Acharya N J Biol Chem. 2021; 298(2):101506.

PMID: 34929163 PMC: 8784325. DOI: 10.1016/j.jbc.2021.101506.

Sequence context effects of replication of Fapy•dG in three mutational hot spot sequences of the p53 gene in human cells.

Bacurio J, Yang H, Naldiga S, Powell B, Ryan B, Freudenthal B DNA Repair (Amst). 2021; 108:103213.

PMID: 34464900 PMC: 8616820. DOI: 10.1016/j.dnarep.2021.103213.

References

Pham P, Bertram J, ODonnell M, Woodgate R, Goodman M . A model for SOS-lesion-targeted mutations in Escherichia coli. Nature. 2001; 409(6818):366-70. DOI: 10.1038/35053116. View

Bailly V, Lauder S, Prakash S, Prakash L . Yeast DNA repair proteins Rad6 and Rad18 form a heterodimer that has ubiquitin conjugating, DNA binding, and ATP hydrolytic activities. J Biol Chem. 1997; 272(37):23360-5. DOI: 10.1074/jbc.272.37.23360. View

Wang Y, Maher V, Mitchell D, McCormick J . Evidence from mutation spectra that the UV hypermutability of xeroderma pigmentosum variant cells reflects abnormal, error-prone replication on a template containing photoproducts. Mol Cell Biol. 1993; 13(7):4276-83. PMC: 359977. DOI: 10.1128/mcb.13.7.4276-4283.1993. View

Waters H, Seetharam S, Seidman M, Kraemer K . Ultraviolet hypermutability of a shuttle vector propagated in xeroderma pigmentosum variant cells. J Invest Dermatol. 1993; 101(5):744-8. DOI: 10.1111/1523-1747.ep12371686. View

Creighton S, Goodman M . Gel kinetic analysis of DNA polymerase fidelity in the presence of proofreading using bacteriophage T4 DNA polymerase. J Biol Chem. 1995; 270(9):4759-74. DOI: 10.1074/jbc.270.9.4759. View

Tan C, Castillo C, So A, Downey K . An auxiliary protein for DNA polymerase-delta from fetal calf thymus. J Biol Chem. 1986; 261(26):12310-6. View

Bloom L, Chen X, Fygenson D, Turner J, ODonnell M, Goodman M . Fidelity of Escherichia coli DNA polymerase III holoenzyme. The effects of beta, gamma complex processivity proteins and epsilon proofreading exonuclease on nucleotide misincorporation efficiencies. J Biol Chem. 1997; 272(44):27919-30. DOI: 10.1074/jbc.272.44.27919. View

Cai J, Gibbs E, Uhlmann F, Phillips B, Yao N, ODonnell M . A complex consisting of human replication factor C p40, p37, and p36 subunits is a DNA-dependent ATPase and an intermediate in the assembly of the holoenzyme. J Biol Chem. 1997; 272(30):18974-81. DOI: 10.1074/jbc.272.30.18974. View

Canella K, Seidman M . Mutation spectra in supF: approaches to elucidating sequence context effects. Mutat Res. 2000; 450(1-2):61-73. DOI: 10.1016/s0027-5107(00)00016-6. View

10.

Echols H, Goodman M . Fidelity mechanisms in DNA replication. Annu Rev Biochem. 1991; 60:477-511. DOI: 10.1146/annurev.bi.60.070191.002401. View

11.

Goodman M, Creighton S, Bloom L, Petruska J . Biochemical basis of DNA replication fidelity. Crit Rev Biochem Mol Biol. 1993; 28(2):83-126. DOI: 10.3109/10409239309086792. View

12.

Warbrick E, Lane D, Glover D, Cox L . A small peptide inhibitor of DNA replication defines the site of interaction between the cyclin-dependent kinase inhibitor p21WAF1 and proliferating cell nuclear antigen. Curr Biol. 1995; 5(3):275-82. DOI: 10.1016/s0960-9822(95)00058-3. View

13.

Washington M, Johnson R, Prakash S, Prakash L . Fidelity and processivity of Saccharomyces cerevisiae DNA polymerase eta. J Biol Chem. 1999; 274(52):36835-8. DOI: 10.1074/jbc.274.52.36835. View

14.

Brash D . Sunlight and the onset of skin cancer. Trends Genet. 1997; 13(10):410-4. DOI: 10.1016/s0168-9525(97)01246-8. View

15.

Johnson R, Prakash S, Prakash L . Efficient bypass of a thymine-thymine dimer by yeast DNA polymerase, Poleta. Science. 1999; 283(5404):1001-4. DOI: 10.1126/science.283.5404.1001. View

16.

Yu S, Johnson R, Prakash S, Prakash L . Requirement of DNA polymerase eta for error-free bypass of UV-induced CC and TC photoproducts. Mol Cell Biol. 2000; 21(1):185-8. PMC: 88792. DOI: 10.1128/MCB.21.1.185-188.2001. View

17.

Thomas D, Roberts J, Sabatino R, Myers T, Tan C, Downey K . Fidelity of mammalian DNA replication and replicative DNA polymerases. Biochemistry. 1991; 30(51):11751-9. DOI: 10.1021/bi00115a003. View

18.

Haracska L, Yu S, Johnson R, Prakash L, Prakash S . Efficient and accurate replication in the presence of 7,8-dihydro-8-oxoguanine by DNA polymerase eta. Nat Genet. 2000; 25(4):458-61. DOI: 10.1038/78169. View

19.

Lee S, Eki T, Hurwitz J . Synthesis of DNA containing the simian virus 40 origin of replication by the combined action of DNA polymerases alpha and delta. Proc Natl Acad Sci U S A. 1989; 86(19):7361-5. PMC: 298061. DOI: 10.1073/pnas.86.19.7361. View

20.

Johnson R, Washington M, Prakash S, Prakash L . Bridging the gap: a family of novel DNA polymerases that replicate faulty DNA. Proc Natl Acad Sci U S A. 1999; 96(22):12224-6. PMC: 34254. DOI: 10.1073/pnas.96.22.12224. View