Crosstalk between the nucleolus and the DNA damage response

Abstract

Nucleolar function and the cellular response to DNA damage have long been studied as distinct disciplines. New research and a new appreciation for proteins holding multiple functional roles, however, is beginning to change the way we think about the crosstalk among distinct cellular processes. Here, we focus on the crosstalk between the DNA damage response and the nucleolus, including a comprehensive review of the literature that reveals a role for conventional DNA repair proteins in ribosome biogenesis, and conversely, ribosome biogenesis proteins in DNA repair. Furthermore, with recent advances in nucleolar proteomics and a growing list of proteins that localize to the nucleolus, it is likely that we will continue to identify new DNA repair proteins with a nucleolar-specific role. Given the importance of ribosome biogenesis and DNA repair in essential cellular processes and the role that they play in diverse pathologies, continued elucidation of the overlap between these two disciplines will be essential to the advancement of both fields and to the development of novel therapeutics.

Extracellular vesicles impose quiescence on residual hematopoietic stem cells in the leukemic niche

“…Given the gains in AML-EV-mediated quiescence in HSC and gains in replating efficiency, we decided to evaluate their DNAdamage response (DDR) [45][46][47]. We observed a consistent increase in cH2AX foci (Fig 6D), indicating the presence of DNA doublestrand breaks, along with the induction of canonical DDR transcripts (including the non-homologous end-joining pathway transcripts) in KSL selected HSPC from AML xenografts relative to controls ( Fig 6E).…”

Unveiling the non-repair face of the Base Excision Repair pathway in RNA processing: A missing link between DNA repair and gene expression?

“…A number of recent interactomic studies significantly contributed to open new scenarios for the comprehension of non-canonical functions of BER proteins, including understanding their unusual distribution in the nucleolar compartment [17,60,61] (Antoniali et al, submitted). The APE1-interactome network, characterized in part in our laboratory and in different literature works, actually comprises more than 100 different protein species whose functions are related to four biological pathways intimately interconnected: DNA repair, Excision Repair, RNA processing and Transcriptional Regulation (Fig.…”

Nuclear phosphatidylinositol 3,4,5-trisphosphate interactome uncovers an enrichment in nucleolar proteins

“…The nucleolus is a compartment where rRNA transcription and processing occur to enable ribosome biogenesis(94). However, gene ontology analyses of nucleolar proteomes showed their association with other biological functions such as cell cycle regulation and DNA repair(94,95). Indeed, a growing body of evidence indicates that some nucleolar proteins have roles in DNA repair(95)(96)(97)(98).…”