title: DNase1L2 degrades nuclear DNA during corneocyte formation.
abstract: The removal of keratinocyte (KC) nuclear DNA by deoxyribonucleases (DNases) is an important step in the formation of normal stratum corneum (SC). However, the molecular identity of the DNA-degrading enzymes has so far remained elusive. Here we show that the endonuclease DNase1-like 2 (DNase1L2) is preferentially expressed in the epidermis and that its expression correlates with terminal differentiation of KC in vitro and in vivo. In biopsies of normal skin, DNase1L2 mRNA was regularly found in suprabasal KC and DNase1L2 protein was highly abundant in the stratum granulosum. In contrast to normal skin, DNase1L2 expression was downregulated in parakeratotic epidermis such as in psoriatic lesions. When DNase1L2 gene expression was knocked down by small interfering RNA in a human skin equivalent model, nuclei were maintained through all layers of the SC. Taken together, our data demonstrate that DNase1L2 plays an essential role in DNA degradation during terminal differentiation of epidermal KC.
authors.affiliation: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Fischer
authors.forename: Leopold
authors.initials: L
authors.lastname: Eckhart
authors.forename: Michael
authors.initials: M
authors.lastname: Mildner
authors.forename: Karin
authors.initials: K
authors.lastname: Jaeger
authors.forename: Maria
authors.initials: M
authors.lastname: Buchberger
authors.forename: Minoo
authors.initials: M
authors.lastname: Ghannadan
authors.forename: Erwin
authors.initials: E
authors.lastname: Tschachler
mesh_terms: D001913:Bowen's Disease / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D003850:Deoxyribonuclease I; D003851:Deoxyribonucleases / Q000235:genetics / Q000502:physiology*; D004706:Endodeoxyribonucleases; D000078404:Epidermal Cells; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D011565:Psoriasis / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D012333:RNA, Messenger; D004247:DNA; D003851:Deoxyribonucleases; D004706:Endodeoxyribonucleases; C107519:DNASE1L2 protein, human; D003850:Deoxyribonuclease I