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PCAT19 safeguards quiescent endothelial DNA by preventing uncontrolled phosphorylation of replication protein A2

ABSTRACT: PCAT19 safeguards quiescent endothelial DNA by preventing uncontrolled phosphorylation of replication protein A2

PROVIDER: PRJNA818329 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18399908.fastq.gz	Fastqsanger.gz
	SRR18399909.fastq.gz	Fastqsanger.gz
	SRR18399910.fastq.gz	Fastqsanger.gz
	SRR18399911.fastq.gz	Fastqsanger.gz
	SRR18399912.fastq.gz	Fastqsanger.gz

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PCAT19 safeguards quiescent endothelial DNA by preventing uncontrolled phosphorylation of replication protein A2

Project description:In healthy vessels, endothelial cells maintain a stable, differentiated and growth-arrested phenotype for years. Upon injury, a rapid phenotypic switch facilitates proliferation to restore tissue perfusion. Here we report the identification of the endothelial cell-enriched long noncoding RNA (lncRNA) PCAT19, which contributes to this process and acts as a safeguard for the endothelial genome during the quiescent phase. PCAT19 is enriched in confluent, quiescent endothelial cells. PCAT19 binds to the full replication protein A (RPA) complex in a DNA damage and cell cycle-related manner. PCAT19 limits phosphorylation of RPA2 on the serine 33 (S33) residue and thereby facilitates the DNA damage response at the expense of slower cell cycle progression. Reduction in PCAT19 levels, either in response to loss of cell contacts or knockdown, promoted endothelial proliferation and angiogenic function. Collectively, PCAT19 acts as a dynamic guardian of the endothelial genome, promotes cellular longevity and facilitates rapid switching to proliferation.

2022-09-23 | GSE199091 | GEO

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Long non-coding RNA PCAT19 safeguards DNA in quiescent endothelial cells by preventing uncontrolled phosphorylation of RPA2.

Project description:In healthy vessels, endothelial cells maintain a stable, differentiated, and growth-arrested phenotype for years. Upon injury, a rapid phenotypic switch facilitates proliferation to restore tissue perfusion. Here we report the identification of the endothelial cell-enriched long non-coding RNA (lncRNA) PCAT19, which contributes to the proliferative switch and acts as a safeguard for the endothelial genome. PCAT19 is enriched in confluent, quiescent endothelial cells and binds to the full replication protein A (RPA) complex in a DNA damage- and cell-cycle-related manner. Our results suggest that PCAT19 limits the phosphorylation of RPA2, primarily on the serine 33 (S33) residue, and thereby facilitates an appropriate DNA damage response while slowing cell cycle progression. Reduction in PCAT19 levels in response to either loss of cell contacts or knockdown promotes endothelial proliferation and angiogenesis. Collectively, PCAT19 acts as a dynamic guardian of the endothelial genome and facilitates rapid switching from quiescence to proliferation.

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