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DNA polymerase ? deficiency causes impaired wound healing and stress-induced skin pigmentation.


ABSTRACT: DNA polymerase ? (pol ?) is a specialized enzyme important for DNA damage tolerance, facilitating synthesis past lesions caused by radiation or chemical damage. Here we report that disruption of Rev3l (encoding the catalytic subunit of pol ?) 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 of Rev3l-proficient melanocytes to the Rev3l-defective epidermis. 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 ? 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.

SUBMITTER: Lange SS 

PROVIDER: S-EPMC6055517 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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DNA polymerase ζ deficiency causes impaired wound healing and stress-induced skin pigmentation.

Lange Sabine S SS   Bhetawal Sarita S   Reh Shelley S   Powell Katherine Leslie KL   Kusewitt Donna F DF   Wood Richard D RD  

Life science alliance 20180629 3


DNA polymerase ζ (pol ζ) is a specialized enzyme important for DNA damage tolerance, facilitating synthesis past lesions caused by radiation or chemical damage. Here we report that disruption of <i>Rev3l</i> (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 m  ...[more]

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