A novel transcript for DNA repair gene Ercc1 in mouse skin

Area of Science:

• Molecular Biology
• Genetics
• Dermatology

Background:

• Nucleotide excision repair (NER) pathway corrects UV-induced DNA damage.
• Skin is highly exposed to UV radiation, necessitating robust DNA repair mechanisms.
• ERCC1 (Excision Repair Cross-Complementation group 1) protein, complexed with XPF, performs crucial endonuclease activity in NER.

Purpose of the Study:

• Investigate if Ercc1 gene expression has unique properties in skin.
• Identify novel transcripts or regulatory mechanisms of Ercc1 in skin.
• Determine the role of skin-specific Ercc1 expression in response to UV damage.

Main Methods:

• Analysis of Ercc1 mRNA expression in mouse skin tissues.
• Comparison of transcript levels between embryonic, neonatal, and adult mice.
• UV irradiation experiments on adult skin and cultured keratinocytes.
• Genotyping and analysis of Ercc1 gene sequence and promoter regions in different mouse strains.
• Use of Ercc1 transgene to map promoter activity.

Main Results:

• A novel, skin-specific Ercc1 mRNA transcript originating from an alternative upstream promoter was identified.
• This transcript's levels increased postnatally but were not induced by UV radiation.
• Higher levels of the skin-specific transcript were observed in albino mouse strains compared to pigmented strains.
• Expression was linked to the Ercc1 gene sequence, specifically a promoter-active transposable element found in albino strains, not coat pigmentation.
• ERCC1 protein levels remained consistent across strains and conditions.

Conclusions:

• A novel skin-specific promoter drives Ercc1 expression in mouse skin, independent of UV exposure.
• The regulation of this skin-specific transcript is influenced by genetic factors, including a transposable element associated with mouse coat color.
• This finding suggests specialized mechanisms for DNA repair gene expression in the skin.