title: Nucleolar responses to DNA double-strand breaks.
abstract: Maintenance of cellular homeostasis is key to prevent transformation and disease. The cellular response to DNA double-strand breaks, primarily orchestrated by the ATM/ATR kinases is one of many mechanisms that serve to uphold genome stability and homeostasis. Upon detection of double-strand breaks (DSBs), several signaling cascades are activated to halt cell cycle progression and initiate repair. Furthermore, the DNA damage response (DDR) controls cellular processes such as transcription, splicing and metabolism. Recent studies have uncovered aspects of how the DDR operates within nucleoli. It appears that the DDR controls transcription in the nucleoli, not only when DNA breaks occur in the rDNA repeats, but also when a nuclear DDR is activated. In addition, we have gained first insights into how repair of DSBs is organized in the nucleolus. Collectively, these recent studies provide a more comprehensive picture of how the DDR regulates basic cellular functions to maintain cellular homeostasis. In this review we will summarize recent findings and discuss their implications for our understanding of how the DDR regulates transcription and repair in the nucleolus.
authors.affiliation: Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen, Denmark dhl@cancer.dk.
authors.forename: Dorthe Helena
authors.identifier: http://orcid.org/0000-0002-8280-1252
authors.initials: DH
authors.lastname: Larsen
authors.affiliation: Department of Gynecology, University of Zurich, Wagistrasse 14, CH-8952 Schlieren, Switzerland dhl@cancer.dk.
authors.forename: Manuel
authors.initials: M
authors.lastname: Stucki
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics* / Q000378:metabolism; D002466:Cell Nucleolus / Q000235:genetics* / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004275:DNA, Ribosomal / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D042822:Genomic Instability; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D004275:DNA, Ribosomal; D004247:DNA; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins