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Molecular and Cellular Biology, May 2000, p. 3522-3528, Vol. 20, No. 10
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Evidence for the Involvement of Nucleotide Excision
Repair in the Removal of Abasic Sites in Yeast
Carlos A.
Torres-Ramos,
Robert E.
Johnson,
Louise
Prakash, and
Satya
Prakash*
Sealy Center for Molecular Science,
University of Texas Medical Branch, Galveston, Texas 77555-1061
Received 20 January 2000/Returned for modification 22 February
2000/Accepted 28 February 2000
In eukaryotes, DNA damage induced by ultraviolet light and other
agents which distort the helix is removed by nucleotide excision repair
(NER) in a fragment ~25 to 30 nucleotides long. In humans, a
deficiency in NER causes xeroderma pigmentosum (XP), characterized by
extreme sensitivity to sunlight and a high incidence of skin cancers.
Abasic (AP) sites are formed in DNA as a result of spontaneous base
loss and from the action of DNA glycosylases involved in base excision
repair. In Saccharomyces cerevisiae, AP sites are removed
via the action of two class II AP endonucleases, Apn1 and Apn2. Here,
we provide evidence for the involvement of NER in the removal of AP
sites and show that NER competes with Apn1 and Apn2 in this repair
process. Inactivation of NER in the apn1
or
apn1
apn2
strain enhances sensitivity to the
monofunctional alkylating agent methyl methanesulfonate and leads to
further impairment in the cellular ability to remove AP sites. A
deficiency in the repair of AP sites may contribute to the internal
cancers and progressive neurodegeneration that occur in XP patients.
*
Corresponding author. Mailing address: Sealy Center for
Molecular Science, University of Texas Medical Branch, 6.104 Medical Research Building, 11th and Mechanic St., Galveston, TX 77555-1061. Phone: (409) 747-8602. Fax: (409) 747-8608. E-mail:
sprakash{at}scms.utmb.edu.
Molecular and Cellular Biology, May 2000, p. 3522-3528, Vol. 20, No. 10
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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