vestnik-bio-msuВестник Московского университета. Серия 16. БиологияVestnik Moskovskogo universiteta. Seriya 16. Biologiya0137-0952Lomonosov Moscow State University, School of Biology10.55959/MSU0137-0952-16-2022-77-4-241-247vestnik-bio-msu-1185Research ArticleОригинальные исследованияВлияние однонитевых разрывов ДНК на транскрипцию нуклеосомEffect of single-strand DNA breaks on transcription of nucleosomeshttps://orcid.org/0000-0002-5048-0378ГерасимоваН. С.GerasimovaN. S.

Герасимова Надежда Сергеевна – канд. биол. наук, ст. науч. сотр. кафедры биоинженерии биологического факультета

Department of Bioengineering, School of Biology

1–12 Leninskie gory, Moscow, 119234

gerasimova@mail.bio.msu.ruАхтарМ. С.AkhtarM. S.

Ахтар Мохаммад Сохаил – PhD, вед. науч. сотр.

Molecular and Structural Biology Division

Lucknow 226031, Uttar Pradesh

sohail@cdri.res.inhttps://orcid.org/0000-0002-7389-7993СтудитскийВ. М.StuditskyV. M.

Студитский Василий Михайлович – докт. биол. наук, вед. науч. сотр. кафедры биоинженерии биологического факультета, профессор Программы эпигенетики рака

Cancer Epigenetics Team

Cottman Avenue 333, Philadelphia, PA 19111

vasily.studitsky@fccc.eduМосковский государственный университет имени М.В. ЛомоносоваРоссияLomonosov Moscow State UniversityRussian FederationCSIR-Central Drug Research InstituteИндияCSIR-Central Drug Research InstituteIndiaМосковский государственный университет имени М.В. Ломоносова, Fox Chase Cancer CenterСоединённые Штаты АмерикиFox Chase Cancer CenterUnited States202230112022774241247Copyright © Герасимова Н.С., Ахтар М.С., Студитский В.М., 20222022Герасимова Н.С., Ахтар М.С., Студитский В.М.Gerasimova N.S., Akhtar M.S., Studitsky V.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestnik-bio-msu.elpub.ru/jour/article/view/1185

Ранее в исследованиях было показано, что однонитевой разрыв нематричной цепи ДНК может вызывать остановку транскрибирующей РНК-полимеразы, но только при организации ДНК в нуклеосому. Наблюдаемый эффект объясняли в рамках модели транскрипции хроматина с образованием внутринуклеосомных петель – интермедиатов, в которых фермент оказывается остановленным в петле ДНК на гистоновом октамере. Согласно указанной модели, разрыв цепи ослабляет возникающее в ходе транскрипции напряжение структуры ДНК, что вызывает стабилизацию ДНК-гистоновых взаимодействий и арест РНК-полимеразы. В данной работе продолжено определение границ таких внутринуклеосомных петель и обнаружено, что образование контактов ДНК с гистонами позади фермента происходит на расстоянии не менее 17 пар нуклеотидов от активного центра.

Previous studies revealed the inhibitory effect of single-stranded breaks in a non-template DNA strand (NT-SSB) on RNA polymerase transcription through the nucleosome. The observed effect was explained within the model of chromatin transcription mechanism with the formation of intranucleosomal DNA loops (i-loops) – intermediates in which the enzyme is locked in the DNA loop on the histone octamer. According to the model, NT-SSBs reduce the tension in the DNA structure caused by transcription and hinders the opening of the i-loop with the enzyme and further elongation. In this work, the boundaries of such i-loops are determined. Nucleosomes with NT-SSBs were transcribed. It was determined that the formation of contacts between DNA and histones behind RNAP occurs at a distance of more than 17 base pairs from the active center of the enzyme.

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The authors declare that there are no conflicts of interest present.