A role for the HOXB7 homeodomain protein in DNA repair

Ethel Rubin, Xinyan Wu, Tao Zhu, Joyce C Y Cheung, Hexin Chen, Annaka Lorincz, Raj K. Pandita, Girdhar G. Sharma, Chol Ha Hyo, Judith Gasson, Les A. Hanakahi, Tej K. Pandita, Saraswati Sukumar

Research output: Contribution to journalArticle

Abstract

Homeobox genes encode transcription factors which function in body axis patterning in the developing embryo. Recent evidence suggests that the maintenance of specific HOX expression patterns is necessary for regulating the homeostasis of adult tissues as well. In this study, HOXB7 transformed human mammary epithelial cells, MCF10A, to grow in minimally supplemented medium, to form colonies in Matrigel, and display resistance to ionizing radiation. Searching for protein partners of HOXB7 that might contribute to resistance to ionizing radiation, we identified four HOXB7-binding proteins by GST pull-down/affinity chromatography and confirmed their interactions by coimmunoprecipitation in vivo. Interestingly, all four HOXB7-binding proteins shared functions as genomic caretakers and included members of the DNA-dependent protein kinase holoenzyme (Ku70, Ku80, DNA-PKcs) responsible for DNA double-strand break repair by nonhomologous end joining pathway and poly(ADP) ribose polymerase. Exogenous and endogenous expression of HOXB7 enhanced nonhomologous end joining and DNA repair functions in vitro and in vivo, which were reversed by silencing HOXB7. This is the first mechanistic study providing definitive evidence for the involvement of any HOX protein in DNA double-strand break repair.

Original languageEnglish (US)
Pages (from-to)1527-1535
Number of pages9
JournalCancer Research
Volume67
Issue number4
DOIs
Publication statusPublished - Feb 15 2007

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Rubin, E., Wu, X., Zhu, T., Cheung, J. C. Y., Chen, H., Lorincz, A., ... Sukumar, S. (2007). A role for the HOXB7 homeodomain protein in DNA repair. Cancer Research, 67(4), 1527-1535. https://doi.org/10.1158/0008-5472.CAN-06-4283