Colocalization, Physical, and Functional Interaction between Werner and Bloom Syndrome Proteins

The RecQ helicase family comprises a conserved group of proteins implicated in several aspects of DNA metabolism. Three of the family members are defective in heritable diseases characterized by abnormal growth, premature aging, and predisposition to malignancies. These include the WRN and BLM gene...

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Bibliographic Details
Published in:The Journal of biological chemistry 2002-06, Vol.277 (24), p.22035-22044
Main Authors: von Kobbe, Cayetano, Karmakar, Parimal, Dawut, Lale, Opresko, Patricia, Zeng, Xianmin, Brosh, Jr, Robert M, Hickson, Ian D, Bohr, Vilhelm A
Format: Article
Language:English
Subjects:
Adenosine Triphosphatases - chemistry
Adenosine Triphosphatases - metabolism
BLM protein
Bloom's syndrome
Blotting, Western
Cell Line
Cell Nucleus - metabolism
DNA Helicases - chemistry
DNA Helicases - metabolism
Enzyme-Linked Immunosorbent Assay
Exodeoxyribonucleases
HeLa Cells
Humans
Microscopy, Fluorescence
Models, Biological
Phenotype
Precipitin Tests
Protein Binding
Protein Structure, Tertiary
Recombinant Proteins - metabolism
RecQ Helicases
RecQ protein
Werner Syndrome Helicase
Werner's syndrome
WRN protein
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Summary:The RecQ helicase family comprises a conserved group of proteins implicated in several aspects of DNA metabolism. Three of the family members are defective in heritable diseases characterized by abnormal growth, premature aging, and predisposition to malignancies. These include the WRN and BLM gene products that are defective in Werner and Bloom syndromes, disorders which share many phenotypic and cellular characteristics including spontaneous genomic instability. Here, we report a physical and functional interaction between BLM and WRN. These proteins were coimmunoprecipitated from a nuclear matrix-solubilized fraction, and the purified recombinant proteins were shown to interact directly. Moreover, BLM and WRN colocalized to nuclear foci in three human cell lines. Two regions of WRN that mediate interaction with BLM were identified, and one of these was localized to the exonuclease domain of WRN. Functionally, BLM inhibited the exonuclease activity of WRN. This is the first demonstration of a physical and functional interaction between RecQ helicases. Our observation that RecQ family members interact provides new insights into the complex phenotypic manifestations resulting from the loss of these proteins.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M200914200