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Suppression of gross chromosomal rearrangements by the multiple functions of the Mre11-Rad50-Xrs2 complex in Saccharomyces cerevisiae.
DNA Repair (Amst). 2005 May 02; 4(5):606-17.DR

Abstract

The Mre11-Rad50-Xrs2 complex in Saccharomyces cerevisiae has roles in the intra-S checkpoint, homologous recombination, non-homologous end joining, meiotic recombination, telomere maintenance and the suppression of gross chromosomal rearrangements (GCRs). The discovery of mutations in the genes encoding the human homologues of two MRX subunits that underlie the chromosome fragility syndromes, Ataxia telangiectasia-like disorder and Nijmegen breakage syndrome suggest that the MRX complex also functions in suppression of GCRs in human cells. Previously, we demonstrated that the deletion mutations in each of the MRX genes increased the rate of GCRs up to 1000-fold compared to wild-type rates. However, it has not been clear which molecular function of the MRX complex is important for suppression of GCRs. Here, we present evidence that at least three different activities of the MRX complex are important for suppression of GCRs. These include the nuclease activity of Mre11, an activity related to MRX complex formation and another activity that has a close link with the telomere maintenance function of the MRX complex. An activity related to MRX complex formation is especially important for the suppression of translocation type of GCRs. However, the non-homologous end joining function of MRX complex does not appear to participate in the suppression of GCRs.

Authors+Show Affiliations

Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive, Bethesda, MD 20892, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15811632

Citation

Smith, Stephanie, et al. "Suppression of Gross Chromosomal Rearrangements By the Multiple Functions of the Mre11-Rad50-Xrs2 Complex in Saccharomyces Cerevisiae." DNA Repair, vol. 4, no. 5, 2005, pp. 606-17.
Smith S, Gupta A, Kolodner RD, et al. Suppression of gross chromosomal rearrangements by the multiple functions of the Mre11-Rad50-Xrs2 complex in Saccharomyces cerevisiae. DNA Repair (Amst). 2005;4(5):606-17.
Smith, S., Gupta, A., Kolodner, R. D., & Myung, K. (2005). Suppression of gross chromosomal rearrangements by the multiple functions of the Mre11-Rad50-Xrs2 complex in Saccharomyces cerevisiae. DNA Repair, 4(5), 606-17.
Smith S, et al. Suppression of Gross Chromosomal Rearrangements By the Multiple Functions of the Mre11-Rad50-Xrs2 Complex in Saccharomyces Cerevisiae. DNA Repair (Amst). 2005 May 2;4(5):606-17. PubMed PMID: 15811632.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Suppression of gross chromosomal rearrangements by the multiple functions of the Mre11-Rad50-Xrs2 complex in Saccharomyces cerevisiae. AU - Smith,Stephanie, AU - Gupta,Amitabha, AU - Kolodner,Richard D, AU - Myung,Kyungjae, PY - 2004/12/06/received PY - 2005/4/7/pubmed PY - 2005/7/29/medline PY - 2005/4/7/entrez SP - 606 EP - 17 JF - DNA repair JO - DNA Repair (Amst) VL - 4 IS - 5 N2 - The Mre11-Rad50-Xrs2 complex in Saccharomyces cerevisiae has roles in the intra-S checkpoint, homologous recombination, non-homologous end joining, meiotic recombination, telomere maintenance and the suppression of gross chromosomal rearrangements (GCRs). The discovery of mutations in the genes encoding the human homologues of two MRX subunits that underlie the chromosome fragility syndromes, Ataxia telangiectasia-like disorder and Nijmegen breakage syndrome suggest that the MRX complex also functions in suppression of GCRs in human cells. Previously, we demonstrated that the deletion mutations in each of the MRX genes increased the rate of GCRs up to 1000-fold compared to wild-type rates. However, it has not been clear which molecular function of the MRX complex is important for suppression of GCRs. Here, we present evidence that at least three different activities of the MRX complex are important for suppression of GCRs. These include the nuclease activity of Mre11, an activity related to MRX complex formation and another activity that has a close link with the telomere maintenance function of the MRX complex. An activity related to MRX complex formation is especially important for the suppression of translocation type of GCRs. However, the non-homologous end joining function of MRX complex does not appear to participate in the suppression of GCRs. SN - 1568-7864 UR - https://www.unboundmedicine.com/medline/citation/15811632/Suppression_of_gross_chromosomal_rearrangements_by_the_multiple_functions_of_the_Mre11_Rad50_Xrs2_complex_in_Saccharomyces_cerevisiae_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1568-7864(05)00030-3 DB - PRIME DP - Unbound Medicine ER -