RMI1 facilitates repair of ionizing radiation–induced DNA damage and maintenance of genomic stability

Abstract

Ionizing radiation (IR) causes a wide variety of DNA lesions, of which DNA double-stranded breaks (DSBs) are the most deleterious. Homologous recombination (HR) is a crucial route responsible for repairing DSBs. RecQ-mediated genome instability protein 1 (RMI1) is a member of an evolutionarily conserved Bloom syndrome complex, which prevents and resolves aberrant recombination products during HR, thereby promoting genome stability. However, little is known about the role of RMI1 in regulating the cellular response to IR. This study aimed to understand the cellular functions and molecular mechanisms by which RMI1 maintains genomic stability after IR exposure. Here, we showed IR upregulated the RMI1 protein level and induced RMI1 relocation to the DNA damage sites. We also demonstrated that the loss of RMI1 in cells resulted in enhanced levels of DNA damage, sustained cell cycle arrest, and impaired HR repair after IR, leading to reduced cell viability and elevated genome instability. Taken together, our results highlighted the direct roles of RMI1 in response to DNA damage induced by IR and implied that RMI1 might be a new genome safeguard molecule to radiation-induced damage.

Anthracyclines induce cardiotoxicity through a shared gene expression response signature

“…ZNF740 is a transcriptional regulator whose DNA binding motifs are associated with enhancer usage in heart failure suggesting that this gene may indeed play a role in cardiotoxicity [ 61 ]. RMI1 facilitates double-stranded break repair and heterodimerizes with TOP3A that has topoisomerase activity in both mitochondria and the nucleus, again suggesting a mechanism behind the association [ 62 , 63 ]. From the adult AC-induced cardiotoxicity GWAS study, our analysis revealed strong effects on the expression of genes including PELI2 and LGALS3 .…”