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

524 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 (US)
Pages (from-to)1015-1019
Number of pages5
JournalNature
Volume406
Issue number6799
DOIs
StatePublished - Aug 31 2000

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DNA-Directed DNA Polymerase
DNA
DNA Replication
Pyrimidine Dimers
Thymine
Eukaryota
Mutagenesis
Saccharomyces cerevisiae
Genes

ASJC Scopus subject areas

  • General

Cite this

Eukaryotic polymerases ι and ζ act sequentially to bypass DNA lesions. / Johnson, Robert E.; Washington, M. Todd; Haracska, Lajos; Prakash, Satya; Prakash, Louise.

In: Nature, Vol. 406, No. 6799, 31.08.2000, p. 1015-1019.

Research output: Contribution to journalArticle

Johnson, Robert E. ; Washington, M. Todd ; Haracska, Lajos ; Prakash, Satya ; Prakash, Louise. / Eukaryotic polymerases ι and ζ act sequentially to bypass DNA lesions. In: Nature. 2000 ; Vol. 406, No. 6799. pp. 1015-1019.
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