title: Essential role of the keratinocyte-specific endonuclease DNase1L2 in the removal of nuclear DNA from hair and nails.
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.
authors.affiliation: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Fischer
authors.forename: Sandra
authors.initials: S
authors.lastname: Szabo
authors.forename: Jennifer
authors.initials: J
authors.lastname: Scherz
authors.forename: Karin
authors.initials: K
authors.lastname: Jaeger
authors.forename: Heidemarie
authors.initials: H
authors.lastname: Rossiter
authors.forename: Maria
authors.initials: M
authors.lastname: Buchberger
authors.forename: Minoo
authors.initials: M
authors.lastname: Ghannadan
authors.forename: Marcela
authors.initials: M
authors.lastname: Hermann
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Theussl
authors.forename: Desmond J
authors.initials: DJ
authors.lastname: Tobin
authors.forename: Erwin F
authors.initials: EF
authors.lastname: Wagner
authors.forename: Erwin
authors.initials: E
authors.lastname: Tschachler
authors.forename: Leopold
authors.initials: L
authors.lastname: Eckhart
mesh_terms: D000818:Animals; D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000502:physiology*; D006197:Hair / Q000378:metabolism*; D006724:Hoof and Claw / Q000378:metabolism*; D015603:Keratinocytes / Q000201:enzymology*; D051379:Mice; D013314:Stress, Mechanical
chemical_list: D004272:DNA, Mitochondrial; D004247:DNA; D003850:Deoxyribonuclease I