Eukaryotic polymerases ι and ζ act sequentially to bypass DNA lesions

Robert E. Johnson, M. Todd Washington, Lajos Haracska, Satya Prakash, Louise Prakash

Research output: Contribution to journalArticle

536 Citations (Scopus)

Abstract

DNA lesions can often block DNA replication, so cells possess specialized low-fidelity, and often error-prone, DNA polymerases that can bypass such lesions and promote replication of damaged DNA. The Saccharomyces cerevisiae RAD30 and human hRAD30A encode Polη, which bypasses a cis-syn thymine-thymine dimer efficiently and accurately. Here we show that a related human gene, hRAD30B, encodes the DNA polymerase Polι, which misincorporates deoxynucleotides at a high rate. To bypass damage, Polι specifically incorporates deoxynucleotides opposite highly distorting or non-instructional DNA lesions. This action is combined with that of DNA polymerase Polζ, which is essential for damage-induced mutagenesis, to complete the lesion bypass. Polζ is very inefficient in inserting deoxynucleotides opposite DNA lesions, but readily extends from such deoxynucleotides once they have been inserted. Thus, in a new model for mutagenic bypass of DNA lesions in eukaryotes, the two DNA polymerases act sequentially: Polι incorporates deoxynucleotides opposite DNA lesions, and Polζ functions as a mispair extender.

Original languageEnglish
Pages (from-to)1015-1019
Number of pages5
JournalNature
Volume406
Issue number6799
DOIs
Publication statusPublished - Aug 31 2000

ASJC Scopus subject areas

  • General

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    Johnson, R. E., Washington, M. T., Haracska, L., Prakash, S., & Prakash, L. (2000). Eukaryotic polymerases ι and ζ act sequentially to bypass DNA lesions. Nature, 406(6799), 1015-1019. https://doi.org/10.1038/35023030