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Interaction between the helicases genetically linked to Fanconi anemia group J and Bloom's syndrome.
Suhasini, Avvaru N; Rawtani, Nina A; Wu, Yuliang; Sommers, Joshua A; Sharma, Sudha; Mosedale, Georgina; North, Phillip S; Cantor, Sharon B; Hickson, Ian D; Brosh, Robert M.
Afiliação
  • Suhasini AN; Laboratory of Molecular Gerontology, National Institute on Aging, NIH, NIH Biomedical Research Center, Baltimore, MD 21224, USA.
EMBO J ; 30(4): 692-705, 2011 Feb 16.
Article em En | MEDLINE | ID: mdl-21240188
ABSTRACT
Bloom's syndrome (BS) and Fanconi anemia (FA) are autosomal recessive disorders characterized by cancer and chromosomal instability. BS and FA group J arise from mutations in the BLM and FANCJ genes, respectively, which encode DNA helicases. In this work, FANCJ and BLM were found to interact physically and functionally in human cells and co-localize to nuclear foci in response to replication stress. The cellular level of BLM is strongly dependent upon FANCJ, and BLM is degraded by a proteasome-mediated pathway when FANCJ is depleted. FANCJ-deficient cells display increased sister chromatid exchange and sensitivity to replication stress. Expression of a FANCJ C-terminal fragment that interacts with BLM exerted a dominant negative effect on hydroxyurea resistance by interfering with the FANCJ-BLM interaction. FANCJ and BLM synergistically unwound a DNA duplex substrate with sugar phosphate backbone discontinuity, but not an 'undamaged' duplex. Collectively, the results suggest that FANCJ catalytic activity and its effect on BLM protein stability contribute to preservation of genomic stability and a normal response to replication stress.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Síndrome de Bloom / Fatores de Transcrição de Zíper de Leucina Básica / Proteínas de Grupos de Complementação da Anemia de Fanconi / RecQ Helicases / Anemia de Fanconi Limite: Animals / Humans Idioma: En Revista: EMBO J Ano de publicação: 2011 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Síndrome de Bloom / Fatores de Transcrição de Zíper de Leucina Básica / Proteínas de Grupos de Complementação da Anemia de Fanconi / RecQ Helicases / Anemia de Fanconi Limite: Animals / Humans Idioma: En Revista: EMBO J Ano de publicação: 2011 Tipo de documento: Article País de afiliação: Estados Unidos