This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Barber, L. J.
Right arrow Articles by McHugh, P. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Barber, L. J.
Right arrow Articles by McHugh, P. J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 2005, p. 2297-2309, Vol. 25, No. 6
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.6.2297-2309.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

DNA Interstrand Cross-Link Repair in the Saccharomyces cerevisiae Cell Cycle: Overlapping Roles for PSO2 (SNM1) with MutS Factors and EXO1 during S Phase

Louise J. Barber,1 Thomas A. Ward,2 John A. Hartley,1 and Peter J. McHugh2*

Cancer Research UK Drug-DNA Interactions Research Group, Department of Oncology, Royal Free and University College Medical School, University College London, London,1 Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom2

Received 20 October 2004/ Returned for modification 16 November 2004/ Accepted 2 December 2004

Pso2/Snm1 is a member of the ß-CASP metallo-ß-lactamase family of proteins that include the V(D)J recombination factor Artemis. Saccharomyces cerevisiae pso2 mutants are specifically sensitive to agents that induce DNA interstrand cross-links (ICLs). Here we establish a novel overlapping function for PSO2 with MutS mismatch repair factors and the 5'-3' exonuclease Exo1 in the repair of DNA ICLs, which is confined to S phase. Our data demonstrate a requirement for NER and Pso2, or Exo1 and MutS factors, in the processing of ICLs, and this is required prior to the repair of ICL-induced DNA double-strand breaks (DSBs) that form during replication. Using a chromosomally integrated inverted-repeat substrate, we also show that loss of both pso2 and exo1/msh2 reduces spontaneous homologous recombination rates. Therefore, PSO2, EXO1, and MSH2 also appear to have overlapping roles in the processing of some forms of endogenous DNA damage that occur at an irreversibly collapsed replication fork. Significantly, our analysis of ICL repair in cells synchronized for each cell cycle phase has revealed that homologous recombination does not play a major role in the direct repair of ICLs, even in G2, when a suitable template is readily available. Rather, we propose that recombination is primarily involved in the repair of DSBs that arise from the collapse of replication forks at ICLs. These findings have led to considerable clarification of the complex genetic relationship between various ICL repair pathways.

* Corresponding author. Mailing address: Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom. Phone: 44-1865-222-441. Fax: 44-1865-222-431. E-mail: peter.mchugh{at}cancer.org.uk.

Molecular and Cellular Biology, March 2005, p. 2297-2309, Vol. 25, No. 6
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.6.2297-2309.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Muniandy, P. A., Thapa, D., Thazhathveetil, A. K., Liu, S.-t., Seidman, M. M. (2009). Repair of Laser-localized DNA Interstrand Cross-links in G1 Phase Mammalian Cells. J. Biol. Chem. 284: 27908-27917 [Abstract] [Full Text]  
  • Zhang, N., Kaur, R., Lu, X., Shen, X., Li, L., Legerski, R. J. (2005). The Pso4 mRNA Splicing and DNA Repair Complex Interacts with WRN for Processing of DNA Interstrand Cross-links. J. Biol. Chem. 280: 40559-40567 [Abstract] [Full Text]  
  • Ahkter, S., Richie, C. T., Zhang, N., Behringer, R. R., Zhu, C., Legerski, R. J. (2005). Snm1-Deficient Mice Exhibit Accelerated Tumorigenesis and Susceptibility to Infection. Mol. Cell. Biol. 25: 10071-10078 [Abstract] [Full Text]  
  • Richards, S., Liu, S.-T., Majumdar, A., Liu, J.-L., Nairn, R. S., Bernier, M., Maher, V., Seidman, M. M. (2005). Triplex targeted genomic crosslinks enter separable deletion and base substitution pathways. Nucleic Acids Res 33: 5382-5393 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»