The nucleolus

Lam, Yun Wah; Trinkle-Mulcahy, Laura; Lamond, Angus I.

doi:10.1242/jcs.01736

Cited by 162 publications

(139 citation statements)

References 26 publications

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“…2). This membraneless organelle is considered a dynamic structure (4,84), where protein complexes are continuously exchanged with the nucleoplasm. Its classical tripartite organization has been dissected using electron microscopy and reflects the different steps of ribosomal biogenesis (130): (i) the fibrillar center, where the RNA polymerase I (Pol I) transcription starts; (ii) the dense fibrillar component, where the initial stages of pre-rRNA processing occur and (iii) the granular component involved in the late processing steps (62).…”

Section: Structure Composition and Classical Functions Of The Nuclementioning

confidence: 99%

Emerging Roles of the Nucleolus in Regulating the DNA Damage Response: The Noncanonical DNA Repair Enzyme APE1/Ref-1 as a Paradigmatical Example

Antoniali

Lirussi

Poletto

et al. 2014

Antioxidants & Redox Signaling

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Significance: An emerging concept in DNA repair mechanisms is the evidence that some key enzymes, besides their role in the maintenance of genome stability, display also unexpected noncanonical functions associated with RNA metabolism in specific subcellular districts (e.g., nucleoli). During the evolution of these key enzymes, the acquisition of unfolded domains significantly amplified the possibility to interact with different partners and substrates, possibly explaining their phylogenetic gain of functions. Recent Advances: After nucleolar stress or DNA damage, many DNA repair proteins can freely relocalize from nucleoli to the nucleoplasm. This process may represent a surveillance mechanism to monitor the synthesis and correct assembly of ribosomal units affecting cell cycle progression or inducing p53-mediated apoptosis or senescence. Critical Issues: A paradigm for this kind of regulation is represented by some enzymes of the DNA base excision repair (BER) pathway, such as apurinic/apyrimidinic endonuclease 1 (APE1). In this review, the role of the nucleolus and the noncanonical functions of the APE1 protein are discussed in light of their possible implications in human pathologies. Future Directions: A productive cross-talk between DNA repair enzymes and proteins involved in RNA metabolism seems reasonable as the nucleolus is emerging as a dynamic functional hub that coordinates cell growth arrest and DNA repair mechanisms. These findings will drive further analyses on other BER proteins and might imply that nucleic acid processing enzymes are more versatile than originally thought having evolved DNA-targeted functions after a previous life in the early RNA world. Antioxid. Redox Signal. 20, 621-639.

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Section: Structure Composition and Classical Functions Of The Nuclementioning

confidence: 99%

Emerging Roles of the Nucleolus in Regulating the DNA Damage Response: The Noncanonical DNA Repair Enzyme APE1/Ref-1 as a Paradigmatical Example

Antoniali

Lirussi

Poletto

et al. 2014

Antioxidants & Redox Signaling

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“…Indeed, the structure of the nucleolus is thought to be determined by protein on-rate versus off-rate ratio. 18 According to this model, nucleophosmin contributes to build-up the nucleolar compartment in which it is one of the most abundant components 20 among the approximately 700 proteins identified by proteomics. 21 In fact, flux of nucleophosmin at the nucleolus-nucleoplasm interface is definitively unbalanced towards the nucleolus.…”

Section: Npm1wt Traffic Between Nucleoplasm and Nucleolusmentioning

confidence: 99%

“…20 When observed at electron microscopy, the nucleolus is morphologically divided into three main components that reflect the multi-step ribosome biogenesis process: the fibrillar centres (containing DNA sequences encoding ribosomal RNA); 38 the dense fibrillar component (in which nascent pre-rRNA transcripts enter to undergo a series of early processing steps); and the granular component, radiating out from the dense fibrillar component, in which intermediate or late stages of RNA maturation occur. 39 Notably, nucleophosmin expression is restricted to the granular component, 20 reflecting its involvement in later processing and assembly steps and in ribosomal subunit export. 40 At first glance, the restricted NPM1wt nucleolar localization appears surprising in the light of its continual shuttling between nucleus and cytoplasm.…”

Section: Native Npm1 Is a Nucleolar Protein With Ubiquitous Tissue Exmentioning

confidence: 99%

Altered nucleophosmin transport in acute myeloid leukaemia with mutated NPM1: molecular basis and clinical implications

et al. 2009

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Nucleophosmin (NPM1) is a highly conserved nucleo-cytoplasmic shuttling protein that shows a restricted nucleolar localization. Mutations of NPM1 gene leading to aberrant cytoplasmic dislocation of nucleophosmin (NPMc þ ) occurs in about one third of acute myeloid leukaemia (AML) patients that exhibit distinctive biological and clinical features. We discuss the latest advances in the molecular basis of nucleophosmin traffic under physiological conditions, describe the molecular abnormalities underlying altered transport of nucleophosmin in NPM1-mutated AML and present evidences supporting the view that cytoplasmic nucleophosmin is a critical event for leukaemogenesis. We then outline how a highly specific immunohistochemical assay can be exploited to diagnose NPM1-mutated AML and myeloid sarcoma in paraffin-embedded samples by looking at aberrant nucleophosmin accumulation in cytoplasm of leukaemic cells. This procedure is also suitable for detection of haemopoietic multilineage involvement in bone marrow trephines. Moreover, use of immunohistochemistry as surrogate for molecular analysis can serve as first-line screening in AML and should facilitate implementation of the 2008 World Health Organization classification of myeloid neoplasms that now incorporates AML with mutated NPM1 (synonym: NPMc þ AML) as a new provisional entity. Finally, we discuss the future therapeutic perspectives aimed at reversing the altered nucleophosmin transport in AML with mutated NPM1.

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“…Before 2002, nearly 120 proteins had been reported to localize in the nucleolus through the methods of biochemical analyses and cellular localization. Now, coupling methods of liquid chromatography and tandem mass spectrometry allow scientists to identify more nucleolar proteins and lead to the coverage of nucleolar protein that is extended to almost 700 in human [38].…”

Section: Proteomic Analyses Of the Nucleolusmentioning

confidence: 99%