A model for transcription-dependent R-loop formation at double-stranded DNA breaks: Implications for their detection and biological effects.

Autor: Belotserkovskii BP; Department of Biology, Stanford University, USA. Electronic address: borpavbel@netscape.net., Hanawalt PC; Department of Biology, Stanford University, USA. Electronic address: hanawalt@stanford.edu.
Jazyk: angličtina
Zdroj: Journal of theoretical biology [J Theor Biol] 2024 Dec 07; Vol. 595, pp. 111962. Date of Electronic Publication: 2024 Oct 09.
DOI: 10.1016/j.jtbi.2024.111962
Abstrakt: R-loops are structures containing an RNA-DNA duplex and an unpaired DNA strand. During R-loop formation an RNA strand invades the DNA duplex, displacing the homologous DNA strand and binding the complementary DNA strand. Here we analyze a model for transcription-dependent R-loop formation at double-stranded DNA breaks (DSBs). In this model, R-loop formation is preceded by detachment of the non-template DNA strand from the RNA polymerase (RNAP). Then, strand exchange is initiated between the nascent RNA and the non-template DNA strand. During that strand exchange the length of the R-loop could either increase, or decrease in a biased random-walk fashion, in which the bias would depend upon the DNA sequence. Eventually, the restoration of the DNA duplex would completely displace the RNA. However, as long as the RNAP remains bound to the template DNA strand it prevents that displacement. Thus, according to the model, RNAPs stalled at DSBs can increase the lifespan of R-loops, increasing their detectability in experiments, and perhaps enhancing their biological effects.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Ltd.)
Databáze: MEDLINE
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