Cockayne Syndrome Type A Protein Protects Primary Human Keratinocytes from Senescence

The Journal of Investigative Dermatology
Sonia CordiscoElena Dellambra

Abstract

Defects in Cockayne syndrome type A (CSA), a gene involved in nucleotide excision repair, cause an autosomal recessive syndrome characterized by growth failure, progressive neurological dysfunction, premature aging, and skin photosensitivity and atrophy. Beyond its role in DNA repair, the CSA protein has additional functions in transcription and oxidative stress response, which are not yet fully elucidated. Here, we investigated the role of CSA protein in primary human keratinocyte senescence. Primary keratinocytes from three patients with CS-A displayed premature aging features, namely premature clonal conversion, high steady-state levels of reactive oxygen species and 8-OH-hydroxyguanine, and senescence-associated secretory phenotype. Stable transduction of CS-A keratinocytes with the wild-type CSA gene restored the normal cellular sensitivity to UV irradiation and normal 8-OH-hydroxyguanine levels. Gene correction was also characterized by proper restoration of keratinocyte clonogenic capacity and expression of clonal conversion key regulators (p16 and p63), decreased NF-κB activity and, in turn, the expression of its targets (NOX1 and MnSOD), and the secretion of senescence-associated secretory phenotype mediators. Overall,...Continue Reading

Citations

Jul 16, 2020·Cells·Marios G KrokidisChryssostomos Chatgilialoglu
Feb 3, 2021·DNA Repair·Alexandra M D'Amico, Karen M Vasquez
Dec 24, 2020·The Journal of Investigative Dermatology·Mansoor HussainVilhelm A Bohr
Nov 25, 2020·Seminars in Cell & Developmental Biology·Gustavo Satoru KajitaniCarlos Frederico Martins Menck
Jun 25, 2021·Mechanisms of Ageing and Development·Chin Yee Ho, Oliver Dreesen
Aug 26, 2021·Antioxidants & Redox Signaling·Clément CrochemoreMiria Ricchetti

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