RNA:DNA hybrids accumulate at DNA double-strand breaks (DSBs) and were shown to regulate homologous recombination repair. The mechanism responsible for the formation of these non-canonical RNA:DNA structures remains unclear although they were proposed to arise consequently to RNA polymerase II or III loading followed by DSB-induced de novo transcription at the break site. Here, we found no evidence of RNA polymerase recruitment at DSBs. Rather, strand-specific R-loop mapping revealed that RNA:DNA hybrids are mainly generated at DSBs occurring in transcribing loci, from the hybridization of pre-existing RNA to the 3′ overhang left by DNA end resection. We further identified the H3K4me3 reader spindlin 1 and the transcriptional regulator PAF1 as factors promoting RNA:DNA hybrid accumulation at DSBs, through their role in mediating transcriptional repression in cis to DSBs. Altogether, we provide evidence that RNA:DNA hybrids accumulate at DSBs occurring in transcribing loci as a result o

PARP inhibitor treatment triggers histone release from the chromatin in cancer cells; consequently, targeting the histone chaperone NASP renders cells vulnerable to PARP inhibition.

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Canal et al. used biochemical reconstitution of DNA replication to show that continued Okazaki fragment synthesis after nucleotide exhaustion depletes PCNA, RFC, and DNA polymerases ε and δ, deprotecting replication forks and impairing restart. By limiting Okazaki fragment generation and factor depletion, the replication checkpoint protects forks, allows restart, and promotes survival.

Structures associated with the final steps of non-homologous end joining (NHEJ) and gap filling present new targets for NHEJ inhibition to enhance efficacy of radiotherapy and accuracy of gene editing...

He is taking self-enrichment to a scale never seen before in America.

Crick group leader Simon Boulton co-founded Artios in 2016, a spin-out from Cancer Research UK’s Commercial Partnerships, where he is now VP of Science Strategy. Artios develops cancer treatments that...

Antagonistic activities of the 53BP1 axis and the tumor suppressor BRCA1-BARD1 determine whether DNA double-strand breaks (DSBs) are repaired by end joining or homologous recombination. We show that t...

Nature - Ku limits RNA-induced innate immunity to allow Alu-expansion in primates

Scientific Reports - Parp1 deletion rescues cerebellar hypotrophy in xrcc1 mutant zebrafish