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. (C) 2010 Elsevier B.V. All rights reserved.
Role of senataxin in DNA damage and telomeric stability / DE AMICIS, Andrea; Piane, Maria; Francesca, Ferrari; Maurizio, Fanciulli; Domenico, Delia; Chessa, Luciana. - In: DNA REPAIR. - ISSN 1568-7864. - 10:2(2011), pp. 199-209. [10.1016/j.dnarep.2010.10.012]
Role of senataxin in DNA damage and telomeric stability
DE AMICIS, ANDREA;PIANE, Maria;CHESSA, Luciana
2011
Abstract
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. (C) 2010 Elsevier B.V. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
