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Some CUT&RUN protocols utilize contaminating E. coli DNA in the pAG-MNase for sample normalization. However, this can become problematic when switching lots of pAG-MNase, because each lot of enzyme will have differing amounts of contaminating DNA. Instead, we recommend using a separate yeast spike-in DNA sample. We provide a yeast spike-in DNA sample with our CUT&RUN Assay Kit #86652 and our CUT&RUN pAG-MNase and Spike-In DNA #40366 for which every lot is tested and optimized for CUT&RUN. This yeast spike-in DNA provides better lot-to-lot consistency for your normalization efforts.