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A POLD3/BLM dependent pathway handles DSBs in transcribed chromatin upon excessive RNA:DNA hybrids accumulation

ABSTRACT: A POLD3/BLM dependent pathway handles DSBs in transcribed chromatin upon excessive RNA:DNA hybrids accumulation

PROVIDER: PRJEB51910 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR9419330.fastq.gz	Fastqsanger.gz
	ERR9419331.fastq.gz	Fastqsanger.gz
	ERR9419332.fastq.gz	Fastqsanger.gz
	ERR9419333.fastq.gz	Fastqsanger.gz
	ERR9419324.fastq.gz	Fastqsanger.gz

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A POLD3/BLM dependent pathway handles DSBs in transcribed chromatin upon excessive RNA:DNA hybrids accumulation

Project description:Transcriptionally active loci are particularly prone to breakage and mounting evidence suggest that DNA Double-Strand Breaks arising in active genes are handled by a dedicated repair pathway, Transcription-Coupled DSB Repair (TC-DSBR), that entails R-loop accumulation and dissolution. Here, we uncovered a function for the Bloom RecQ DNA helicase (BLM) in TC-DSBR in human cells. BLM is recruited in a transcription dependent-manner at DSBs where it fosters resection, RAD51 binding and accurate Homologous Recombination repair. However, in an R-loop dissolution-deficient background, we found that BLM promotes cell death. We report that upon excessive R-loop accumulation, DNA synthesis is enhanced at DSBs, in a anner that depends on BLM and POLD3. Altogether our work unveils a role for BLM at DSBs in active chromatin, and highlights the toxic potential of RNA:DNA hybrids that accumulate at transcription-associated DSBs.

2022-04-13 | E-MTAB-11592 | biostudies-arrayexpress

A POLD3/BLM dependent pathway handles DSBs in transcribed chromatin upon excessive RNA:DNA hybrid accumulation.

Project description:Transcriptionally active loci are particularly prone to breakage and mounting evidence suggests that DNA Double-Strand Breaks arising in active genes are handled by a dedicated repair pathway, Transcription-Coupled DSB Repair (TC-DSBR), that entails R-loop accumulation and dissolution. Here, we uncover a function for the Bloom RecQ DNA helicase (BLM) in TC-DSBR in human cells. BLM is recruited in a transcription dependent-manner at DSBs where it fosters resection, RAD51 binding and accurate Homologous Recombination repair. However, in an R-loop dissolution-deficient background, we find that BLM promotes cell death. We report that upon excessive RNA:DNA hybrid accumulation, DNA synthesis is enhanced at DSBs, in a manner that depends on BLM and POLD3. Altogether our work unveils a role for BLM at DSBs in active chromatin, and highlights the toxic potential of RNA:DNA hybrids that accumulate at transcription-associated DSBs.

| S-EPMC9019021 | biostudies-literature

Blm

Project description:Rattus norvegicus Blm, BLM RecQ like helicase [Source:RGD Symbol;Acc:1308810], is expressed in 5 baseline experiment(s);

| ENSRNOG00000011213 | ExpressionAtlas

Blm

Project description:Rattus norvegicus Blm, BLM RecQ like helicase [Source:RGD Symbol;Acc:1308810], is differentially expressed in 23 experiment(s);

| ENSRNOG00000011213 | ExpressionAtlas

BLM

Project description:Monodelphis domestica BLM, BLM RecQ like helicase [Source:NCBI gene;Acc:100014352], is expressed in 2 baseline experiment(s);

| ENSMODG00000019449 | ExpressionAtlas

BLM

Project description:Sus scrofa BLM, BLM RecQ like helicase [Source:VGNC Symbol;Acc:VGNC:96569], is differentially expressed in 2 experiment(s);

| ENSSSCG00000001816 | ExpressionAtlas

BLM

Project description:Equus caballus BLM, BLM RecQ like helicase [Source:VGNC Symbol;Acc:VGNC:57212], is expressed in 1 baseline experiment(s);

| ENSECAG00000011405 | ExpressionAtlas

BLM

Project description:Homo sapiens BLM, BLM RecQ like helicase [Source:HGNC Symbol;Acc:HGNC:1058], is expressed in 44 baseline experiment(s);

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BLM

Project description:Sus scrofa BLM, BLM RecQ like helicase [Source:VGNC Symbol;Acc:VGNC:96569], is expressed in 2 baseline experiment(s);

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BLM

Project description:Macaca mulatta BLM, BLM RecQ like helicase [Source:VGNC Symbol;Acc:VGNC:70254], is expressed in 3 baseline experiment(s);

| ENSMMUG00000019526 | ExpressionAtlas

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