RAS, cellular senescence and transformation: The BRCA1 DNA repair pathway at the crossroads

Zhigang Tu, Katherine M. Aird, Rugang Zhang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The definition of an oncogene is a gene that actively promotes tumorigenesis. For example, activation of RAS oncogene promotes cell transformation and cancer. Paradoxically, in primary mammalian cells, oncogenic RAS typically triggers cellular senescence, a state of irreversible cell growth arrest. Oncogene-induced senescence is an important tumor suppression mechanism in vivo. Here, we discuss our recent evidence that RAS-induced suppression of DNA repair response via dissociation of BRCA1 from chromatin promotes senescence while predisposing cells to senescence bypass and transformation by allowing for secondary hits. The molecular mechanism we uncovered helps reconcile the tumor-promoting nature of oncogenic RAS with the tumor-suppressing role of oncogene-induced senescence.

Original languageEnglish (US)
Pages (from-to)1-5
Number of pages5
JournalSmall GTPases
Volume3
Issue number3
StatePublished - Jan 1 2012

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Cell Aging
Oncogenes
DNA Repair
Tumors
Repair
DNA
Neoplasms
Cell growth
Chromatin
Genes
Chemical activation
Cells
Carcinogenesis
Growth

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology

Cite this

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RAS, cellular senescence and transformation : The BRCA1 DNA repair pathway at the crossroads. / Tu, Zhigang; Aird, Katherine M.; Zhang, Rugang.

In: Small GTPases, Vol. 3, No. 3, 01.01.2012, p. 1-5.

Research output: Contribution to journalArticle

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