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Molecular and Cellular Biology, March 2001, p. 1656-1661, Vol. 21, No. 5
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.5.1656-1661.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

3'-Phosphodiesterase and 3'right-arrow 5' Exonuclease Activities of Yeast Apn2 Protein and Requirement of These Activities for Repair of Oxidative DNA Damage

Ildiko Unk, Lajos Haracska, Satya Prakash, and Louise Prakash*

Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, Texas 77555-1061

Received 26 October 2000/Returned for modification 16 November 2000/Accepted 28 November 2000

In Saccharomyces cerevisiae, the AP endonucleases encoded by the APN1 and APN2 genes provide alternate pathways for the removal of abasic sites. Oxidative DNA-damaging agents, such as H2O2, produce DNA strand breaks which contain 3'-phosphate or 3'-phosphoglycolate termini. Such 3' termini are inhibitory to synthesis by DNA polymerases. Here, we show that purified yeast Apn2 protein contains 3'-phosphodiesterase and 3'right-arrow5' exonuclease activities, and mutation of the active-site residue Glu59 to Ala in Apn2 inactivates both these activities. Consistent with these biochemical observations, genetic studies indicate the involvement of APN2 in the repair of H2O2-induced DNA damage in a pathway alternate to APN1, and the Ala59 mutation inactivates this function of Apn2. From these results, we conclude that the ability of Apn2 to remove 3'-end groups from DNA is paramount for the repair of strand breaks arising from the reaction of DNA with reactive oxygen species.

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

Molecular and Cellular Biology, March 2001, p. 1656-1661, Vol. 21, No. 5
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.5.1656-1661.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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