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Genes 2017, 8(6), 158;

The Dual Roles of MYC in Genomic Instability and Cancer Chemoresistance

Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
Tumor Signaling and Angiogenesis Program, Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA
Biochemistry and Cancer Biology Program, The Graduate School, Augusta University, Augusta, GA 30912, USA
Author to whom correspondence should be addressed.
Academic Editor: Selvarangan Ponnazhagan
Received: 28 February 2017 / Revised: 31 May 2017 / Accepted: 1 June 2017 / Published: 7 June 2017
(This article belongs to the Special Issue MYC Networks)
Full-Text   |   PDF [616 KB, uploaded 7 June 2017]   |  


Cancer is associated with genomic instability and aging. Genomic instability stimulates tumorigenesis, whereas deregulation of oncogenes accelerates DNA replication and increases genomic instability. It is therefore reasonable to assume a positive feedback loop between genomic instability and oncogenic stress. Consistent with this premise, overexpression of the MYC transcription factor increases the phosphorylation of serine 139 in histone H2AX (member X of the core histone H2A family), which forms so-called γH2AX, the most widely recognized surrogate biomarker of double-stranded DNA breaks (DSBs). Paradoxically, oncogenic MYC can also promote the resistance of cancer cells to chemotherapeutic DNA-damaging agents such as cisplatin, clearly implying an antagonistic role of MYC in genomic instability. In this review, we summarize the underlying mechanisms of the conflicting functions of MYC in genomic instability and discuss when and how the oncoprotein exerts the contradictory roles in induction of DSBs and protection of cancer-cell genomes. View Full-Text
Keywords: MYC; genomic instability; chemoresistance; γH2AX MYC; genomic instability; chemoresistance; γH2AX

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Kumari, A.; Folk, W.P.; Sakamuro, D. The Dual Roles of MYC in Genomic Instability and Cancer Chemoresistance. Genes 2017, 8, 158.

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