Role of senataxin in DNA damage and telomeric stability

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• 作者：Andrea De Amicis^a ; ^{andrea.deamicis@uniroma1.it} ; Maria Piane^a ; ^{maria.piane@uniroma1.it} ; Francesca Ferrari^a ; ^{f.ferrari@live.it} ; Maurizio Fanciulli^b ; ^{fanciulli@ifo.it} ; Domenico Delia^c ; ^{domenico.delia@istitutotumori.mi.it} ; Luciana Chessa^a ; ^{luciana.chessa@uniroma1.it}
• 关键词：AOA2 ; SETX ; Helicase domain ; DNA damage ; Telomere ; Neurodegeneration
• 刊名：DNA Repair
• 出版年：2011
• 出版时间：7 February 2011
• 年：2011
• 卷：10
• 期：2
• 页码：199-209
• 全文大小：1675 K

文摘

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive neurodegenerative disorder characterized by cerebellar ataxia and oculomotor apraxia. The gene mutated in AOA2, SETX, encodes senataxin (SETX), a putative DNA/RNA helicase. The presence of the helicase domain led us to investigate whether SETX might play a role in DNA damage repair and telomere stability. We analyzed the response of AOA2 lymphocytes and lymphoblasts after treatment with camptothecin (CPT), mitomycin C (MMC), H₂O₂ and X-rays by cytogenetic and Q-FISH (quantitative-FISH) assays. The rate of chromosomal aberrations was normal in AOA2 cells after treatment with CPT, MMC, H₂O₂ and X-rays. Conversely, Q-FISH analysis showed constitutively reduced telomere length in AOA2 lymphocytes, compared to age-matched controls. Furthermore, CPT- or X-ray-induced telomere shortening was more marked in AOA2 than in control cells. The partial co-localization of SETX with telomeric DNA, demonstrated by combined immunofluorescence–Q-FISH and chromatin immunoprecipitation, suggests a possible involvement of SETX in telomere stability.