Melanoma cells express elevated levels of phosphorylated histone H2AX foci

Raymond L. Warters, Patrick J. Adamson, Christopher D. Pond, Sancy Leachman

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

When human cells sustain a DNA double-strand break (dsb), histone H2AX in chromatin surrounding the DNA break is phosphorylated, marking repair foci. The number of phosphorylated histone H2AX (γH2AX) foci approximates the number of dsb present in the cell's nuclear DNA. We observed 0.4 γH2AX foci per nucleus in primary human melanocytes. In contrast, in four melanoma cell lines, we detected 7-17 γH2AX foci per nucleus, a 17-42 times increase in the basal level of γH2AX foci in melanoma cells relative to melanocytes (MC). Thus, untreated melanoma cells express significantly greater numbers of γH2AX foci than do untreated MC. Detection and rejoining of ionizing radiation-induced DNA dsb proceeded as rapidly in melanoma cells as in MC. Melanoma cells, however, reduced the number of radiation-induced γH2AX foci down only to pre-irradiation levels. Co-localization of the majority of γH2AX foci with ataxia telangiectasia mutated, BRCA1, 53BP1, and Nbs1 foci in untreated melanoma cells indicated that the additional foci in melanoma cells were associated with a DNA change that the cells interpret as DNA dsb. Co-localization of γH2AX foci with the telomere replication factor 1 protein in untreated melanoma cells indicates that the additional foci in untreated melanoma cells are associated with dysfunctional telomeres that induce a DNA damage stress response.

Original languageEnglish (US)
Pages (from-to)807-817
Number of pages11
JournalJournal of Investigative Dermatology
Volume124
Issue number4
DOIs
StatePublished - Apr 2005
Externally publishedYes

Fingerprint

Histones
Melanoma
DNA
Melanocytes
Double-Stranded DNA Breaks
Cells
Telomere
Ionizing radiation
Chromatin
Ataxia Telangiectasia
Repair
DNA Breaks
Irradiation
Radiation
Ionizing Radiation
DNA Damage
Cell Line
Proteins

Keywords

  • γH2AX foci
  • Chromosome instability
  • Melanocyte
  • Micronuclei
  • Telomere dysfunction

ASJC Scopus subject areas

  • Dermatology

Cite this

Melanoma cells express elevated levels of phosphorylated histone H2AX foci. / Warters, Raymond L.; Adamson, Patrick J.; Pond, Christopher D.; Leachman, Sancy.

In: Journal of Investigative Dermatology, Vol. 124, No. 4, 04.2005, p. 807-817.

Research output: Contribution to journalArticle

Warters, Raymond L. ; Adamson, Patrick J. ; Pond, Christopher D. ; Leachman, Sancy. / Melanoma cells express elevated levels of phosphorylated histone H2AX foci. In: Journal of Investigative Dermatology. 2005 ; Vol. 124, No. 4. pp. 807-817.
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