---
title: "Should I size select or fragment my CUT&RUN DNA before library prep?"
slug: "should-i-size-select-or-fragment-my-cutrun-dna-before-library-prep"
updated: 2025-11-25T20:47:12Z
published: 2025-11-25T20:47:12Z
canonical: "support.epicypher.com/should-i-size-select-or-fragment-my-cutrun-dna-before-library-prep"
---

> ## Documentation Index
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# Should I size select or fragment my CUT&RUN DNA before library prep?

Shearing and/or size selection of CUT&RUN-enriched DNA is NOT required nor recommended for several reasons:

- The output of CUT&RUN is mainly mononucleosome-sized DNA fragments, making it unneccessary to shear DNA.
- CUT&RUN DNA yields are very low (vs. ChIP). Additional shearing and size selection risks loss of target-enriched DNA.
- During CUT&RUN library prep, there is a clean-up step to remove adapter dimers. This step will also help to retain CUT&RUN-specific fragments.
- The library prep PCR parameters specifically amplify adapter-ligated fragments from 200-700 bp, eliminating larger DNA fragments from the library.
- Large fragments generated by CUT&RUN and observed in final libraries are typically nonspecific background. Shearing DNA at earlier steps would include them in library prep, diluting on-target signal and increasing background.