Journal article
Eukaryotic polymerases ι and ζ act sequentially to bypass DNA lesions
Nature (London), Vol.406(6799), pp.1015-1019
08/31/2000
DOI: 10.1038/35023030
PMID: 10984059
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 Pol eta, which bypasses a cis-syn thymine-thymine dimer efficiently and accurately. Here we show that a related human gene, hRAD30B, encodes the DNA polymerase Pol iota, which misincorporates deoxynucleotides at a high rate. To bypass damage, Pol iota specifically incorporates deoxynucleotides opposite highly distorting or non-instructional DNA lesions. This action is combined with that of DNA polymerase Pol zeta, which is essential for damage-induced mutagenesis, to complete the lesion bypass. Pol zeta 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: Pol iota incorporates deoxynucleotides opposite DNA lesions, and Pol zeta functions as a mispair extender.
Details
- Title: Subtitle
- Eukaryotic polymerases ι and ζ act sequentially to bypass DNA lesions
- Creators
- Robert E Johnson - Sealy Centre for Molecular Science, University of Texas Medical Branch at Galveston, 77555-1061, USAM Todd WashingtonLajos HaracskaSatya PrakashLouise Prakash
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.406(6799), pp.1015-1019
- Publisher
- England
- DOI
- 10.1038/35023030
- PMID
- 10984059
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Language
- English
- Date published
- 08/31/2000
- Academic Unit
- Radiation Oncology; Biochemistry and Molecular Biology
- Record Identifier
- 9984025396502771
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