Cockayne syndrome pathogenesis: Lessons from mouse models

Modeling the Study of DNA Damage Responses in Mice

“…On the other hand, whereas CS is also caused by mutations in some NER genes, classically in ERCC8 and ERCC6, CS patients are more prone to accelerate ageing than cancer (Natale, 2011). A number of mouse models with mutations in NER genes have been developed presenting a broad spectrum of symptoms resembling XP and CS (Jaarsma et al, 2013). Noteworthy, different mutations on the very same NER gene can be pro-cancer or proageing, further illustrating the intimate connection between these two outcomes.…”

Regulation of active genome integrity and expression by Rad26p

“…[1][2][3][4][5] Mutations in CSB lead to defective TCR, physiologically reflected as a severe disorder called CS. 6 Symptoms of CS include premature aging, photosensistivity, cataracts, retinal degeneration, dental caries, hearing loss, muscular and skeletal abnormalities, and progressive decline in neurological and cognitive functions. 6 Prognosis of CS in humans is degenerative and terminal illness with death by the average age of 12 years.…”

“…6 Symptoms of CS include premature aging, photosensistivity, cataracts, retinal degeneration, dental caries, hearing loss, muscular and skeletal abnormalities, and progressive decline in neurological and cognitive functions. 6 Prognosis of CS in humans is degenerative and terminal illness with death by the average age of 12 years. The CSB gene, mutated in about 80% of the CS patients, plays an important role in TCR.…”

Papel das proteínas XPD e DNA polimerase eta nas respostas de células humanas a danos no genoma

“…(65% dos casos) ; em geral mutações em CSA estão associadas aos fenópicos mais brandos (tipos I e III), enquanto as mutações em CSB levam à forma mais grave da doença (Jaarsma et al, 2013). Mutações nos genes CS também podem levar à uma síndrome mais grave, denominada síndrome cérebro-óculo-fácio-esquelética (COFS), assim como a uma síndrome muito branda conhecida como síndrome UV-sensível (UVSS).…”

“…O camundongo Xpd TTD apresenta pelos curtos, quebradiços e deficientes em cisteína, anormalidades na pele, perda de gordura subcutânea e níveis reduzidos de hemáceas, entretanto apresenta anormalidades neurológicas leves (Jaarsma et al, 2013). O camundongo Xpd XPCS/TTD mostra que há uma espécie de dominância de um alelo sobre outro que varia nos diferentes tecidos: o camundongo apresenta diminuição da sensibilidade à luz UV e surgimento de tumores de pele, assim como diminuição dos sintomas típicos de TTD ( Van de Ven et al, 2012).…”