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In DNA-binding proteins, restriction enzymes predominate. The majority of proteins that bind to DNA would be very negatively charged.

DNA-binding proteins include nucleases, which cut DNA molecules, different polymerases, transcription factors, which control the process of transcription, and histones, which are involved in chromosome packing and transcription in the cell nucleus. Zinc finger, helix-turn-helix, leucine zipper, and other nucleic acid-binding domains can all be found in DNA-binding proteins, among many others. There are other more bizarre examples, including effectors that resemble transcription activators. In order to have a specific or general affinity for single- or double-stranded DNA, proteins with DNA-binding domains are known as DNA-binding proteins. Because the primary groove of B-DNA exposes more functional groups that identify a given sequence, sequence-specific DNA-binding proteins typically interact with chromosomes.

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