Paracrine regulation of melanocyte genomic stability: a focus on nucleotide excision repair

Stuart Gordon Jarrett, Katharine Marie Carter, John August D'Orazio

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations

Abstract

UV radiation is a major environmental risk factor for the development of melanoma by causing DNA damage and mutations. Resistance to UV damage is largely determined by the capacity of melanocytes to respond to UV injury by repairing mutagenic photolesions. The nucleotide excision repair (NER) pathway is the major mechanism by which cells correct UV photodamage. This multistep process involves the basic steps of damage recognition, isolation, localized strand unwinding, assembly of a repair complex, excision of the damage-containing strand 3′ and 5′ to the photolesion, synthesis of a sequence-appropriate replacement strand, and finally ligation to restore continuity of genomic DNA. In melanocytes, the efficiency of NER is regulated by several hormonal pathways including the melanocortin and endothelin signaling pathways. Elucidating molecular mechanisms by which melanocyte DNA repair is regulated offers the possibility of developing novel melanoma-preventive strategies to reduce UV mutagenesis, especially in UV-sensitive melanoma-prone individuals.

Original languageEnglish
Pages (from-to)284-293
Number of pages10
JournalPigment Cell and Melanoma Research
Volume30
Issue number3
DOIs
StatePublished - May 2017

Bibliographical note

Funding Information:
We are grateful for support from the National Cancer Institute (R01 CA131075), the Melanoma Research Alliance (MRA), and the Regina Drury Endowment for Pediatric Research. We also acknowledge the technical support of the Markey Research Communications Office and NCI Cancer Center Support Grant (P30 CA177558) of the Markey Cancer Center at the University of Kentucky.

Publisher Copyright:
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Keywords

  • UV photodamage
  • endothelin receptor signaling
  • melanocortin signaling
  • mutagenesis
  • nucleotide excision repair

ASJC Scopus subject areas

  • Oncology
  • Biochemistry, Genetics and Molecular Biology (all)
  • Dermatology

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