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    Essential Role of the Keratinocyte-Specific Endonuclease DNase1L2 in the Removal of Nuclear DNA from Hair and Nails.

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    Publication date
    2011-06
    Author
    Fischer, H.
    Szabo, S.
    Scherz, J.
    Jaeger, K.
    Rossiter, H.
    Buchberger, M.
    Ghannadan, M.
    Hermann, M.
    Theussl, H-C.
    Tobin, Desmond J.
    Wagner, E.F.
    Tschachler, E.
    Eckhart, L.
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    Keyword
    Keratinocyte-Specific Endonuclease DNase1L2; Nuclear DNA; Hair; Nails; Keratinocytes / corneocytes; Stratum corneum
    Peer-Reviewed
    yes
    
    Metadata
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    Abstract
    Degradation of nuclear DNA is a hallmark of programmed cell death. Epidermal keratinocytes die in the course of cornification to function as the dead building blocks of the cornified layer of the epidermis, nails, and hair. Here, we investigated the mechanism and physiological function of DNA degradation during cornification in vivo. Targeted deletion of the keratinocyte-specific endonuclease DNase1-like 2 (DNase1L2) in the mouse resulted in the aberrant retention of DNA in hair and nails, as well as in epithelia of the tongue and the esophagus. In contrast to our previous studies in human keratinocytes, ablation of DNase1L2 did not compromise the cornified layer of the epidermis. Quantitative PCRs showed that the amount of nuclear DNA was dramatically increased in both hair and nails, and that mitochondrial DNA was increased in the nails of DNase1L2-deficient mice. The presence of nuclear DNA disturbed the normal arrangement of structural proteins in hair corneocytes and caused a significant decrease in the resistance of hair to mechanical stress. These data identify DNase1L2 as an essential and specific regulator of programmed cell death in skin appendages, and demonstrate that the breakdown of nuclear DNA is crucial for establishing the full mechanical stability of hair.
    URI
    http://hdl.handle.net/10454/7450
    Version
    No full-text available in the repository
    Citation
    Fischer H, Szabo S, Scherz J, Jaeger K, Rossiter H, Buchberger M, Ghannadan M, Hermann M, Theussl HC, Tobin DJ, Wagner EF, Tschachler E and Eckhart L (2011) Essential role of the keratinocyte-specific endonuclease DNase1L2 in the removal of nuclear DNA from hair and nails. Journal of Investigative Dermatology, 131 (6): 1208-1215.
    Link to publisher’s version
    https://doi.org/10.1038/jid.2011.13
    Type
    Article
    Collections
    Life Sciences Publications

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