Predicting stability of DNA bulge at mononucleotide microsatellite

dc.citation.firstpage7901
dc.citation.issueNumber14
dc.citation.journalTitleNucleic Acids Research
dc.citation.lastpage7908
dc.citation.volumeNumber49
dc.contributor.authorBae, Jin H.
dc.contributor.authorZhang, David Yu
dc.contributor.orgSystems, Synthetic, and Physical Biology
dc.date.accessioned2021-09-21T15:37:53Z
dc.date.available2021-09-21T15:37:53Z
dc.date.issued2021
dc.description.abstractMononucleotide microsatellites are clinically and forensically crucial DNA sequences due to their high mutability and abundance in the human genome. As a mutagenic intermediate of an indel in a microsatellite and a consequence of probe hybridization after such mutagenesis, a bulge with structural degeneracy sliding within a microsatellite is formed. Stability of such dynamic bulges, however, is still poorly understood despite their critical role in cancer genomics and neurological disease studies. In this paper, we have built a model that predicts the thermodynamics of a sliding bulge at a microsatellite. We first identified 40 common bulge states that can be assembled into any sliding bulges, and then characterized them with toehold exchange energy measurement and the partition function. Our model, which is the first to predict the free energy of sliding bulges with more than three repeats, can infer the stability penalty of a sliding bulge of any sequence and length with a median prediction error of 0.22 kcal/mol. Patterns from the prediction clearly explain landscapes of microsatellites observed in the literature, such as higher mutation rates of longer microsatellites and C/G microsatellites.
dc.identifier.citationBae, Jin H. and Zhang, David Yu. "Predicting stability of DNA bulge at mononucleotide microsatellite." <i>Nucleic Acids Research,</i> 49, no. 14 (2021) Oxford University Press: 7901-7908. https://doi.org/10.1093/nar/gkab616.
dc.identifier.digitalgkab616
dc.identifier.doihttps://doi.org/10.1093/nar/gkab616
dc.identifier.urihttps://hdl.handle.net/1911/111390
dc.language.isoeng
dc.publisherOxford University Press
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/),
dc.titlePredicting stability of DNA bulge at mononucleotide microsatellite
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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