Essential role of the keratinocyte-specific endonuclease DNase1L2 in the removal of nuclear DNA from hair and nails.
Essential role of the keratinocyte-specific endonuclease DNase1L2 in the removal of nuclear DNA from hair and nails.
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DOI：
10.1038/jid.2011.13
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发表时间：
2011-06
影响因子：
6.5
通讯作者：
Eckhart, Leopold
中科院分区：
文献类型：
--
作者：
Fischer, Heinz;Szabo, Sandra;Scherz, Jennifer;Jaeger, Karin;Rossiter, Heidemarie;Buchberger, Maria;Ghannadan, Minoo;Hermann, Marcela;Theussl, Hans-Christian;Tobin, Desmond J.;Wagner, Erwin F.;Tschachler, Erwin;Eckhart, Leopold
核DNA的降解是程序性细胞死亡的标志。表皮角质形成细胞在角化过程中死亡，作为表皮、指甲和毛发的角质层的死亡构件。本文研究了玉米角化过程中DNA降解的机制及其生理功能。在小鼠中定向删除角质细胞特异性核酸内切酶DNase1L2导致毛发和指甲以及舌头和食道上皮中DNA的异常保留。与我们以前在人角质形成细胞中的研究相反，DNase1L2的消融不会损害表皮的角质层。定量PCR显示，DNA酶1L2缺陷小鼠的头发和指甲中的核DNA量显著增加，指甲中的线粒体DNA也增加。细胞核DNA的存在扰乱了头发角质细胞中结构蛋白的正常排列，并导致头发对机械应力的抵抗力显著下降。这些数据确定DNase1L2作为皮肤附件中程序性细胞死亡的重要和特异性调节剂，并证明核DNA的分解对于建立毛发的完全机械稳定性至关重要。
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 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.
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