DNA Polymerase Ζ Deficiency Causes Impaired Wound Healing and Stress-Induced Skin Pigmentation

DNA polymerase ζ (pol ζ) is well established as a specialized enzyme important for DNA damage tolerance, facilitating DNA synthesis past lesions caused by radiation or chemical damage. We report that disruption ofRev3l(encoding the catalytic subunit of pol ζ) in mouse epidermis leads to a defect in proliferation that impairs cutaneous wound healing. A striking increase in epidermal skin pigmentation accompanied both wound healing and UV irradiation in these mice. This was a consequence of stress-induced migration ofRev3l-proficient melanocytes to theRev3l-defective epidermis. We found that this pigmentation corresponded with p53 activation in keratinocytes and was absent in p53-negative areas of the epidermis. Expression of the kit ligand (Kitl) gene, a p53-controlled mediator of keratinocyte to melanocyte signaling, was enhanced during wound healing or following UV irradiation. This study extends the function of pol ζ to the process of proliferation during wound healing.Rev3l-deficient epidermis may be a useful mouse model system for examining communication between damaged keratinocytes and melanocytes, including signaling relevant to human disease.