Mph1p promotes gross chromosomal rearrangement through partial inhibition of homologous recombination

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

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34 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1083-1093
Number of pages11
JournalJournal of Cell Biology
Volume181
Issue number7
DOIs
Publication statusPublished - 2008 Jun 30

All Science Journal Classification (ASJC) codes

  • Cell Biology

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    Banerjee, S., Smith, S., Oum, J. H., Liaw, H. J., Hwang, J. Y., Sikdar, N., Motegi, A., Sang, E. L., & Myung, K. (2008). Mph1p promotes gross chromosomal rearrangement through partial inhibition of homologous recombination. Journal of Cell Biology, 181(7), 1083-1093. https://doi.org/10.1083/jcb.200711146