Nucleic Acids Research, Vol 27, Issue 4 956-962, Copyright © 1999 by Oxford University Press
X Wu and Z Wang
Yeast Rad27 is a 5'-->3' exonuclease and a flap endo-nuclease. Apn1 is
the major apurinic/apyrimidinic (AP) endonuclease in yeast. The rad27
deletion mutants are highly sensitive to methylmethane sulfonate (MMS). By
examining the role of Rad27 in different modes of DNA excision repair, we
wish to understand why the cytotoxic effect of MMS is dramatically enhanced
in the absence of Rad27. Base excision repair (BER) of uracil-containing
DNA was deficient in rad27 mutant extracts in that (i) the Apn1 activity
was reduced, and (ii) after DNA incision by Apn1, hydrolysis of 1-5
nucleotides 3' to the baseless sugar phosphate was deficient. Thus, some AP
sites may lead to unprocessed DNA strand breaks in rad27 mutant cells. The
severe MMS sensitivity of rad27 mutants is not caused by a reduction of the
Apn1 activity. Surprisingly, we found that Apn1 endonuclease sensitizes
rad27 mutant cells to MMS. Deleting the APN1 gene largely restored the
resistance of rad27 mutants to MMS. These results suggest that unprocessed
DNA strand breaks at AP sites are mainly responsible for the MMS
sensitivity of rad27 mutants. In contrast, nucleotide excision repair and
BER of oxidative damage were not affected in rad27 mutant extracts,
indicating that Rad27 is specifically required for BER of AP sites in DNA.
ARTICLES
Relationships between yeast Rad27 and Apn1 in response to apurinic/apyrimidinic (AP) sites in DNA
Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  I.-t. Cho, D.-h. Kim, Y.-H. Kang, C.-H. Lee, T. Amangyelid, T. A. Nguyen, J. Hurwitz, and Y.-S. Seo Human Replication Factor C Stimulates Flap Endonuclease 1 J. Biol. Chem., April 17, 2009; 284(16): 10387 - 10399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Ma, V. Panduri, J. F. Sterling, B. Van Houten, D. A. Gordenin, and M. A. Resnick The Transition of Closely Opposed Lesions to Double-Strand Breaks during Long-Patch Base Excision Repair Is Prevented by the Coordinated Action of DNA Polymerase {delta} and Rad27/Fen1 Mol. Cell. Biol., March 1, 2009; 29(5): 1212 - 1221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Ma, M. A. Resnick, and D. A. Gordenin Apn1 and Apn2 endonucleases prevent accumulation of repair-associated DNA breaks in budding yeast as revealed by direct chromosomal analysis Nucleic Acids Res., April 1, 2008; 36(6): 1836 - 1846. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Seiple, P. Jaruga, M. Dizdaroglu, and J. T. Stivers Linking uracil base excision repair and 5-fluorouracil toxicity in yeast Nucleic Acids Res., January 10, 2006; 34(1): 140 - 151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Soustelle, L. Vernis, K. Freon, A. Reynaud-Angelin, R. Chanet, F. Fabre, and M. Heude A New Saccharomyces cerevisiae Strain with a Mutant Smt3-Deconjugating Ulp1 Protein Is Affected in DNA Replication and Requires Srs2 and Homologous Recombination for Its Viability Mol. Cell. Biol., June 15, 2004; 24(12): 5130 - 5143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Callahan, K. J. Andrews, V. A. Zakian, and C. H. Freudenreich Mutations in Yeast Replication Proteins That Increase CAG/CTG Expansions Also Increase Repeat Fragility Mol. Cell. Biol., November 1, 2003; 23(21): 7849 - 7860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sabourin, J. L. Nitiss, K. C. Nitiss, K. Tatebayashi, H. Ikeda, and N. Osheroff Yeast recombination pathways triggered by topoisomerase II-mediated DNA breaks Nucleic Acids Res., August 1, 2003; 31(15): 4373 - 4384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Kelley, Y. W. Kow, and D. M. Wilson III Disparity between DNA Base Excision Repair in Yeast and Mammals: Translational Implications Cancer Res., February 1, 2003; 63(3): 549 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Chang, M. Bellaoui, C. Boone, and G. W. Brown A genome-wide screen for methyl methanesulfonate-sensitive mutants reveals genes required for S phase progression in the presence of DNA damage PNAS, December 24, 2002; 99(26): 16934 - 16939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Matsuzaki, N. Adachi, and H. Koyama Vertebrate cells lacking FEN-1 endonuclease are viable but hypersensitive to methylating agents and H2O2 Nucleic Acids Res., July 15, 2002; 30(14): 3273 - 3277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Debrauwere, S. Loeillet, W. Lin, J. Lopes, and A. Nicolas Links between replication and recombination in Saccharomyces cerevisiae: A hypersensitive requirement for homologous recombination in the absence of Rad27 activity PNAS, July 17, 2001; 98(15): 8263 - 8269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wu, D. Guo, F. Yuan, and Z. Wang Accessibility of DNA polymerases to repair synthesis during nucleotide excision repair in yeast cell-free extracts Nucleic Acids Res., July 15, 2001; 29(14): 3123 - 3130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Alleva and P. W. Doetsch The nature of the 5'-terminus is a major determinant for DNA processing by Schizosaccharomyces pombe Rad2p, a FEN-1 family nuclease Nucleic Acids Res., August 1, 2000; 28(15): 2893 - 2901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. McHugh, W. R. Sones, and J. A. Hartley Repair of Intermediate Structures Produced at DNA Interstrand Cross-Links in Saccharomyces cerevisiae Mol. Cell. Biol., May 15, 2000; 20(10): 3425 - 3433. [Abstract] [Full Text]
|
|
|
|
|
|
R. Gary, M. S. Park, J. P. Nolan, H. L. Cornelius, O. G. Kozyreva, H. T. Tran, K. S. Lobachev, M. A. Resnick, and D. A. Gordenin A Novel Role in DNA Metabolism for the Binding of Fen1/Rad27 to PCNA and Implications for Genetic Risk Mol. Cell. Biol., August 1, 1999; 19(8): 5373 - 5382. [Abstract] [Full Text] [PDF]
|
|