Location of Repository

Mph1p promotes gross chromosomal rearrangement through partial inhibition of homologous recombination

By Soma Banerjee, Stephanie Smith, Ji-Hyun Oum, Hung-Jiun Liaw, Ji-Young Hwang, Nilabja Sikdar, Akira Motegi, Sang Eun Lee and Kyungjae Myung


Gross chromosomal rearrangement (GCR) is a type of genomic instability associated with many cancers. In yeast, multiple pathways cooperate to suppress GCR. In a screen for genes that promote GCR, we identified MPH1, which encodes a 3′–5′ DNA helicase. Overexpression of Mph1p in yeast results in decreased efficiency of homologous recombination (HR) as well as delayed Rad51p recruitment to double-strand breaks (DSBs), which suggests that Mph1p promotes GCR by partially suppressing HR. A function for Mph1p in suppression of HR is further supported by the observation that deletion of both mph1 and srs2 synergistically sensitize cells to methyl methanesulfonate-induced DNA damage. The GCR-promoting activity of Mph1p appears to depend on its interaction with replication protein A (RPA). Consistent with this observation, excess Mph1p stabilizes RPA at DSBs. Furthermore, spontaneous RPA foci at DSBs are destabilized by the mph1Δ mutation. Therefore, Mph1p promotes GCR formation by partially suppressing HR, likely through its interaction with RPA

Topics: Research Articles
Publisher: The Rockefeller University Press
OAI identifier: oai:pubmedcentral.nih.gov:2442200
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles



    1. (2006). Control of translocations between highly diverged genes by Sgs1, the Saccharomyces cerevisiae homolog of the Bloom ’ s syndrome protein.
    2. (2002). Deregulated G1-cyclin expression induces genomic instability by preventing effi cient pre-RC formation.
    3. (2004). Global mapping of the yeast genetic interaction network. Science .
    4. (2004). Junction of RecQ helicase biochemistry and human disease.
    5. (2000). MPH1, a yeast gene encoding a DEAH protein, plays a role in protection of the genome from spontaneous and chemically induced damage.
    6. (2004). Mrc1 is required for sister chromatid cohesion to aid in recombination repair of spontaneous damage.
    7. (2005). Multiple numerical chromosome aberrations in cancer: what are their causes and what are their consequences?
    8. (2004). Mutaor genes for suppression of gross chromosomal rearrangements identifi ed by a genome-wide screening in Saccharoymces cerevisiae.
    9. (2000). Pif1p helicase, a catalytic inhibitor of telomerase in yeast.
    10. (2002). Role of RAD52 epistasis group genes in homologous recombination and double-strand break repair.
    11. (1997). Rules of donor preference in Saccharomyces mating-type gene switching revealed by a competition assay involving two types of recombination.
    12. (2005). Saccharomyces cerevisiae MPH1 gene, required for homologous recombination-mediated mutation avoidance, encodes a 3 to 5 DNA helicase.
    13. (2006). Suppression of gross chromosomal rearrangements by yKu70-yKu80 heterodimer through DNA damage checkpoints.
    14. (1994). The Saccharomyces PIF1 DNA helicase inhibits telomere elongation and de novo telomere formation.
    15. (2005). The yeast chromatin remodeler RSC complex facilitates end joining repair of DNA doublestrand breaks.
    16. (1989). Yeast intrachromosomal recombination: long gene conversion tracts are preferentially associated with reciprocal exchange and require the RAD1 and RAD3 gene products.
    17. (2004). Yeast MPH1 gene functions in an error-free DNA damage bypass pathway that requires genes from homologous recombination, but not from postreplicative repair.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.