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Effect of single-strand DNA breaks on transcription of nucleosomes

https://doi.org/10.55959/MSU0137-0952-16-2022-77-4-241-247

Abstract

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.

About the Authors

N. S. Gerasimova
Lomonosov Moscow State University
Russian Federation

Department of Bioengineering, School of Biology

1–12 Leninskie gory, Moscow, 119234



M. S. Akhtar
CSIR-Central Drug Research Institute
India

Molecular and Structural Biology Division

Lucknow 226031, Uttar Pradesh



V. M. Studitsky
Fox Chase Cancer Center
United States

Cancer Epigenetics Team

Cottman Avenue 333, Philadelphia, PA 19111



References

1. Tubbs A., Nussenzweig A. Endogenous DNA damage as a source of genomic instability in cancer // Cell. 2017. Vol. 168. N 4. P. 644‒656.

2. Caldecott K.W. DNA single-strand break repair and human genetic disease // Trends Cell Biol. 2022. Vol. 32. N 9. P. 733‒745.

3. McKinnon P.J., Caldecott K.W. DNA strand break repair and human genetic disease // Annu. Rev. Genomics Hum. Genet. 2007. Vol. 8. P. 37‒55.

4. Zhou W., Doetsch P.W. Effects of abasic sites and DNA single-strand breaks on prokaryotic RNA polymerases // Proc. Natl. Acad. Sci. U.S.A. 1993. Vol. 90. N 14. P. 6601‒6605.

5. Kathe S.D., Shen G.P., Wallace S.S. Single-stranded breaks in DNA but not oxidative DNA base damages block transcriptional elongation by RNA polymerase II in HeLa cell nuclear extracts // J. Biol. Chem. 2004. Vol. 279. N 18. P. 18511‒18520.

6. Neil A.J., Belotserkovskii B.P., Hanawalt P.C. Transcription blockage by bulky end termini at single-strand breaks in the DNA template: differential effects of 5’ and 3’ adducts // Biochemistry. 2012. Vol. 51. N 44. P. 8964‒8970.

7. Li S., Smerdon M.J. Dissecting transcription-coupled and global genomic repair in the chromatin of yeast GAL1- 10 genes // J. Biol. Chem. 2004. Vol. 279. N 14. P. 14418‒14426.

8. Pestov N.A., Gerasimova N.S., Kulaeva O.I., Studitsky V.M. Structure of transcribed chromatin is a sensor of DNA damage // Sci. Adv. 2015. Vol. 1. N 6: e1500021.

9. Luger K., Mäder A.W., Richmond R.K., Sargent D.F., Richmond T.J. Crystal structure of the nucleosome core particle at 2.8 A resolution // Nature. 1997. Vol. 389. N 6648. P. 251‒260.

10. Hartzog G.A., Speer J.L., Lindstrom D.L. Transcript elongation on a nucleoprotein template // Biochim. Biophys. Acta. 2002. Vol. 1577. N 2. P. 276‒286.

11. Gerasimova N.S., Pestov N.A., Kulaeva O.I., Clark D.J., Studitsky V.M. Transcription-induced DNA supercoiling: New roles of intranucleosomal DNA loops in DNA repair and transcription // Transcription. 2016. Vol. 7. N 3. P. 91‒95.

12. Lowary P.T., Widom J. New DNA sequence rules for high affinity binding to histone octamer and sequencedirected nucleosome positioning // J. Mol. Biol. 1998. Vol. 276. N 1. P. 19‒42.

13. Artsimovitch I., Svetlov V., Murakami K.S., Landick R. Co-overexpression of Escherichia coli RNA polymerase subunits allows isolation and analysis of mutant enzymes lacking lineage-specific sequence insertions // J. Biol. Chem. 2003. Vol. 278. N 14. P. 12344‒12355.

14. Thastrom A., Lowary P.T., Widlund H.R., Cao H., Kubista M., Widom J. Sequence motifs and free energies of selected natural and non-natural nucleosome positioning DNA sequences // J. Mol. Biol. 1999. Vol. 288. N 2. P. 213‒229.

15. Bondarenko V.A., Steele L.M., Ujvari A., Gaykalova D.A., Kulaeva O.I., Polikanov Y.S., Luse D.S., Studitsky V.M. Nucleosomes can form a polar barrier to transcript elongation by RNA polymerase II // Mol. Cell. 2006. Vol. 24. N 3. P. 469‒479.

16. Chang H.W., Kulaeva O.I., Shaytan A.K., Kibanov M., Kuznedelov K., Severinov K.V., Kirpichnikov M.P., Clark D.J., Studitsky V.M. Analysis of the mechanism of nucleosome survival during transcription // Nucleic Acids Res. 2014. Vol. 42. N 3. P. 1619‒1627.

17. Kulaeva O.I., Gaykalova D.A., Pestov N.A., Golovastov V.V., Vassylyev D.G., Artsimovitch I., Studitsky V.M. Mechanism of chromatin remodeling and recovery during passage of RNA polymerase II // Nat. Struct. Mol. Biol. 2009. Vol. 16. N 12. P. 1272‒1278.

18. Walter W., Kireeva M.L., Studitsky V.M., Kashlev M. Bacterial polymerase and yeast polymerase II use similar mechanisms for transcription through nucleosomes // J. Biol. Chem. 2003. Vol. 278. N 38. P. 36148‒36156.

19. Ausio J., Seger D., Eisenberg H. Nucleosome core particle stability and conformational change. Effect of temperature, particle and NaCl concentrations, and crosslinking of histone H3 sulfhydryl groups // J. Mol. Biol. 1984. Vol. 176. N 1. P. 77‒104.

20. Bancaud A., Wagner G., Conde E.S.N., Lavelle C., Wong H., Mozziconacci J., Barbi M., Sivolob A., Le Cam E., Mouawad L., Viovy J.L., Victor J.M., Prunell A. Nucleosome chiral transition under positive torsional stress in single chromatin fibers // Mol. Cell. 2007. Vol. 27. N 1. P. 135‒147.

21. Lilley D.M. DNA opens up – supercoiling and heavy breathing // Trends Genet. 1988. Vol. 4. N 4. P. 111‒114.


Review

For citations:


Gerasimova N.S., Akhtar M.S., Studitsky V.M. Effect of single-strand DNA breaks on transcription of nucleosomes. Vestnik Moskovskogo universiteta. Seriya 16. Biologiya. 2022;77(4):241-247. (In Russ.) https://doi.org/10.55959/MSU0137-0952-16-2022-77-4-241-247

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