Interaction between the helicases genetically linked to Fanconi anemia group J and Bloom's syndrome.

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.

• Authors: Avvaru N Suhasini, Nina A Rawtani, Yuliang Wu, Joshua A Sommers, Sudha Sharma, Georgina Mosedale, Phillip S North, Sharon B Cantor, Ian D Hickson, Robert M Brosh Jr
• Journal: The EMBO journal (EMBO J) Vol. 30 Issue 4 Pg. 692-705 (Feb 16 2011) ISSN: 1460-2075 [Electronic] England
• PMID: 21240188 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• BACH1 protein, human
• Basic-Leucine Zipper Transcription Factors
• Fanconi Anemia Complementation Group Proteins
• Bloom syndrome protein
• DNA Helicases
• RecQ Helicases

Topics

• Animals
• Basic-Leucine Zipper Transcription Factors (genetics, metabolism)
• Bloom Syndrome (genetics)
• Cell Nucleus (metabolism)
• Cells, Cultured
• DNA Helicases (genetics, metabolism, physiology)
• DNA Replication (genetics, physiology)
• Fanconi Anemia (genetics)
• Fanconi Anemia Complementation Group Proteins (genetics, metabolism)
• Genomic Instability (genetics)
• HeLa Cells
• Humans
• Insecta
• Protein Binding (physiology)
• Protein Interaction Mapping
• RecQ Helicases (genetics, metabolism)
• Tissue Distribution