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Molecular and Cellular Biology, August 2004, p. 6900-6906, Vol. 24, No. 16
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.16.6900-6906.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Efficient and Error-Free Replication past a Minor-Groove N2-Guanine Adduct by the Sequential Action of Yeast Rev1 and DNA Polymerase {zeta}

M. Todd Washington,1,{dagger} Irina G. Minko,1,{ddagger} Robert E. Johnson,1 Lajos Haracska,1,§ Thomas M. Harris,2 R. Stephen Lloyd,1,{ddagger} Satya Prakash,1 and Louise Prakash1*

Sealy Center for Molecular Science, University of Texas Medical Branch at Galveston, Galveston, Texas 77555-1061,1 Center in Molecular Toxicology, Department of Chemistry, Vanderbilt University, Nashville, Tennessee 372352

Received 15 April 2004/ Returned for modification 14 May 2004/ Accepted 19 May 2004

Rev1, a member of the Y family of DNA polymerases, functions in lesion bypass together with DNA polymerase {zeta} (Pol{zeta}). Rev1 is a highly specialized enzyme in that it incorporates only a C opposite template G. While Rev1 plays an indispensable structural role in Pol{zeta}-dependent lesion bypass, the role of its DNA synthetic activity in lesion bypass has remained unclear. Since interactions of DNA polymerases with the DNA minor groove contribute to the nearly equivalent efficiencies and fidelities of nucleotide incorporation opposite each of the four template bases, here we examine the possibility that unlike other DNA polymerases, Rev1 does not come into close contact with the minor groove of the incipient base pair, and that enables it to incorporate a C opposite the N2-adducted guanines in DNA. To test this idea, we examined whether Rev1 could incorporate a C opposite the {gamma}-hydroxy-1,N2-propano-2'deoxyguanosine DNA minor-groove adduct, which is formed from the reaction of acrolein with the N2 of guanine. Acrolein, an {alpha},ß-unsaturated aldehyde, is generated in vivo as the end product of lipid peroxidation and from other oxidation reactions. We show here that Rev1 efficiently incorporates a C opposite this adduct from which Pol{zeta} subsequently extends, thereby completing the lesion bypass reaction. Based upon these observations, we suggest that an important role of the Rev1 DNA synthetic activity in lesion bypass is to incorporate a C opposite the various N2-guanine DNA minor-groove adducts that form in DNA.

* Corresponding author. Mailing address: Sealy Center for Molecular Science, University of Texas Medical Branch at Galveston, 6.104 Blocker Medical Research Building, 11th and Mechanic St., Galveston, TX 77555-1061. Phone: (409) 747-8601. Fax: (409) 747-8608. E-mail: l.prakash{at}utmb.edu.

{dagger} Present address: Department of Biochemistry, University of Iowa, Iowa City, IA 52242-1109.

{ddagger} Present address: Center for Research in Occupational and Environmental Toxicology, Oregon Health and Science University, Portland, OR 97239.

§ Present address: Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary H-6701.

Molecular and Cellular Biology, August 2004, p. 6900-6906, Vol. 24, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.16.6900-6906.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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