Function of RecQ helicases in genome stability

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In humans there are five RecQ helicases whereas in simpler organisms there are only one. It is of great interest to explore how these RecQ helicases function individually and together and whether there is abundancy of helicase function or whether each play an individual role. There may be circumstances where they can function in a synergistic manner and this would be informative about whether these different RecQ helicases interact with each other and also about the biological importance of certain processes. We and other groups find that the human RecQ helicases participate in DNA repair, and more specifically in certain subpathways of DNA repair. Three of the RecQ helicases are deficient in disorders of premature aging: Werner syndrome, Bloom syndrome and Rothmund Thomson syndrome. Much less is known about the Rothmund-Thomson syndrome protein, RECQ4, and RecQ5 than about the other human RecQ helicases. We find that the RecQ4 protein participates in DNA repair of double and single strand breaks and that cells from individuals with this condition are defective in DNA repair. Biochemically, we are characterizing the RECQ4 protein and while its helicase function in many ways is similar to those of the WRN and BLM helicases, there are also significant differences. Moreover, we are currently exploring potential the protein interactions and protein complexes that RECQ4 participates in. RecQ5 is another member of the RecQ family for which little information is known. We have previously reported that WRN, BLM and RecQ4 can stimulate core base excision repair proteins. Thus we are evaluating whether RecQ5 can also stimulate and interact with BER proteins.