The dual roles of MYC in genomic instability and cancer chemoresistance

Alpana Kumari, Watson P. Folk, Daitoku Sakamuro

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number158
JournalGenes
Volume8
Issue number6
DOIs
StatePublished - Jun 7 2017

Fingerprint

Genomic Instability
Neoplasms
Double-Stranded DNA Breaks
Histones
Cytoprotection
Oncogene Proteins
DNA Replication
Oncogenes
Serine
Cisplatin
Carcinogenesis
Transcription Factors
Biomarkers
Phosphorylation
Genome
DNA

Keywords

  • Chemoresistance
  • Genomic instability
  • MYC
  • γH2AX

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

The dual roles of MYC in genomic instability and cancer chemoresistance. / Kumari, Alpana; Folk, Watson P.; Sakamuro, Daitoku.

In: Genes, Vol. 8, No. 6, 158, 07.06.2017.

Research output: Contribution to journalReview article

Kumari, Alpana ; Folk, Watson P. ; Sakamuro, Daitoku. / The dual roles of MYC in genomic instability and cancer chemoresistance. In: Genes. 2017 ; Vol. 8, No. 6.
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