Colocalization, physical, and functional interaction between Werner and Bloom syndrome proteins.

Abstract	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.
Authors	Cayetano von Kobbe, Parimal Karmakar, Lale Dawut, Patricia Opresko, Xianmin Zeng, Robert M Brosh Jr, Ian D Hickson, Vilhelm A Bohr
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 277 Issue 24 Pg. 22035-44 (Jun 14 2002) ISSN: 0021-9258 [Print] United States
PMID	11919194 (Publication Type: Journal Article)
Chemical References	Recombinant Proteins Exodeoxyribonucleases Adenosine Triphosphatases Bloom syndrome protein RECQL protein, human DNA Helicases RecQ Helicases WRN protein, human Werner Syndrome Helicase
Topics	Adenosine Triphosphatases (chemistry, metabolism) Blotting, Western Cell Line Cell Nucleus (metabolism) DNA Helicases (chemistry, metabolism) Enzyme-Linked Immunosorbent Assay Exodeoxyribonucleases HeLa Cells Humans Microscopy, Fluorescence Models, Biological Phenotype Precipitin Tests Protein Binding Protein Structure, Tertiary RecQ Helicases Recombinant Proteins (metabolism) Werner Syndrome Helicase

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