4.5 Article

Homologous pairing in short double-stranded DNA- grafted colloidal microspheres

Journal

BIOPHYSICAL JOURNAL
Volume 121, Issue 24, Pages 4819-4829

Publisher

CELL PRESS
DOI: 10.1016/j.bpj.2022.09.037

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Funding

  1. National Science Foundation
  2. [1654599]
  3. [1610783]
  4. [1725984]

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Homologous pairing (HP) is a fundamental biological process that is not fully understood. This study reveals that HP can occur in short DNA sequences as small as 18 basepairs. By analyzing crystal formation in a colloidal micro-particle-based system, the impact of nucleotide order and triplet framework on HP is validated.
Homologous pairing (HP), i.e., the pairing of similar or identical double-stranded DNA, is an insufficiently under-stood fundamental biological process. HP is now understood to also occur without protein mediation, but crucial mechanistic details remain poorly established. Unfortunately, systematic studies of sequence dependence are not practical due to the enor-mous number of nucleotide permutations and multiple possible conformations involved in existing biophysical strategies even when using as few as 150 basepairs. Here, we show that HP can occur in DNA as short as 18 basepairs in a colloidal micro-particle-based system. Exemplary systematic studies include resolving opposing reports of the impact of % AT composition, validating the impact of nucleotide order and triplet framework and revealing isotropic bendability to be crucial for HP. These studies are enabled by statistical analysis of crystal size and fraction within coexisting fluid-crystal phases of double-stranded DNA-grafted colloidal microspheres, where crystallization is predicated by HP.

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