RNA-DNA hybrids on protein coding genes are stabilized by loss of RNase H and are associated with DNA damages during S-phase in fission yeast.

Autor: Sagi T; Genome Dynamics Project, Department of Basic Medical Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan., Sadato D; Clinical Research and Trials Center, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan., Takayasu K; Genome Dynamics Project, Department of Basic Medical Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.; Department of Biosciences, School of Science, Kitasato University, Sagamihara, Kanagawa, Japan., Sasanuma H; Genome Dynamics Project, Department of Basic Medical Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan., Kanoh Y; Genome Dynamics Project, Department of Basic Medical Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan., Masai H; Genome Dynamics Project, Department of Basic Medical Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Jazyk: angličtina
Zdroj: Genes to cells : devoted to molecular & cellular mechanisms [Genes Cells] 2024 Nov; Vol. 29 (11), pp. 966-982. Date of Electronic Publication: 2024 Sep 09.
DOI: 10.1111/gtc.13157
Abstrakt: RNA-DNA hybrid is a part of the R-loop which is an important non-standard nucleic acid structure. RNA-DNA hybrid/R-loop causes genomic instability by inducing DNA damages or inhibiting DNA replication. It also plays biologically important roles in regulation of transcription, replication, recombination and repair. Here, we have employed catalytically inactive human RNase H1 mutant (D145N) to visualize RNA-DNA hybrids and map their genomic locations in fission yeast cells. The RNA-DNA hybrids appear as multiple nuclear foci in rnh1∆rnh201∆ cells lacking cellular RNase H activity, but not in the wild-type. The majority of RNA-DNA hybrid loci are detected at the protein coding regions and tRNA. In rnh1∆rnh201∆ cells, cells with multiple Rad52 foci increase during S-phase and about 20% of the RNA-DNA hybrids overlap with Rad52 loci. During S-phase, more robust association of Rad52 with RNA-DNA hybrids was observed in the protein coding region than in M-phase. These results suggest that persistent RNA-DNA hybrids in the protein coding region in rnh1∆rnh201∆ cells generate DNA damages during S-phase, potentially through collision with DNA replication forks.
(© 2024 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)
Databáze: MEDLINE
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