Dental Management of a 14-Year-Old with Cockayne Syndrome under General Anesthesia

Cockayne’s syndrome is a rare, autosomal recessive disorder characterized clinically by cachectic dwarfism, cutaneous photosensitivity, loss of adipose tissue, mental retardation, skeletal and neurological abnormalities, and pigmentary degeneration of the retina. Dental caries is a common finding. Dental rehabilitation of a 14-year-old male with Cockayne’s syndrome is presented.

Late Activation of Stress Kinases (SAPK/JNK) by Genotoxins Requires the DNA Repair Proteins DNA-PKcs and CSB

Although genotoxic agents are powerful inducers of stress kinases (SAPK/JNK), the contribution of DNA damage itself to this response is unknown. Therefore, SAPK/JNK activation of cells harboring specific defects in DNA damage-recognition mechanisms was studied. Dual phosphorylation of SAPK/JNK by the genotoxin methyl methanesulfonate (MMS) occurred in two waves. The early response (≤2 h after exposure) was similar in cells knockout for ATM, PARP, p53, and CSB or defective in DNA-PKcs compared with wild-type cells. The late response however (≥4 h), was drastically reduced in DNA-PKcs and Cockayne's syndrome B (CSB)-deficient cells. Similar results were obtained with human cells lacking DNA-PKcs and CSB. Activation of SAPK/JNK by MMS was not affected upon inhibition of base excision repair (BER), indicating base damage itself does not signal to SAPK/JNK. Because SAPK/JNK activation was attenuated in nongrowing cells, DNA replication-dependent processing of lesions, involving DNA-PKcs and CSB, appears to be required. DNA-PKcs coprecipitates with SEK1/MKK4 and SAPK/JNK, supporting a role of DNA-PKcs in SAPK/JNK activation. In this process, Rho GTPases are involved since inhibition of Rho impairs MMS-induced signaling to SAPK/JNK. The data show that sensing of DNA damage by DNA-PKcs and CSB causes a delayed SEK1/MKK4-mediated dual phosphorylation of SAPK/JNK.