L’équipe Palancade a publié un nouvel article dans Nature Communications :
DNA lesions can frequently precede DNA:RNA hybrid accumulation
Résumé :
While DNA:RNA hybrids contribute to multiple genomic transactions, their unscheduled formation is a recognized source of DNA lesions. Here, through a suite of systematic screens, we rather observed that a wide range of yeast mutant situations primarily triggering DNA damage actually leads to hybrid accumulation. Focusing on Okazaki fragment processing, we establish that genic hybrids can actually form as a consequence of replication-born discontinuities such as unprocessed flaps or unligated Okazaki fragments. Strikingly, such “post-lesion” DNA:RNA hybrids neither detectably contribute to genetic instability, nor disturb gene expression, as opposed to “pre-lesion” hybrids formed upon defective mRNA biogenesis, e.g., in THO complex mutants. Post-lesion hybrids similarly arise in distinct genomic instability situations, triggered by pharmacological or genetic manipulation of DNA-dependent processes, both in yeast and human cells. Altogether, our data establish that the accumulation of transcription-born DNA:RNA hybrids can occur as a consequence of various types of natural or pathological DNA lesions, yet do not necessarily aggravate their genotoxicity.
Mangione RM, Pierce S, Zheng M, Martin RM, Goncalves C, Kumar A, Scaglione S, de Sousa Morgado C, Penzo A, Lancrey A, Reid RJD, Lautier O, Gaillard PH, Stirling PC, de Almeida SF, Rothstein R, Palancade B. DNA lesions can frequently precede DNA:RNA hybrid accumulation. Nat Commun. 2025 Mar 10;16(1):2401. doi: 10.1038/s41467-025-57588-x. PMID: 40064914.