Nucleolar DNA: the host and the guests

Smirnov, Evgeny; Cmarko, Dušan; Mazel, Tomáš; Hornáček, Matúš; Raška, Ivan

doi:10.1007/s00418-016-1407-x

Cited by 31 publications

(23 citation statements)

References 235 publications

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“…Its primary function is in the making of ribosomes, and it forms in response to the transcription of the ribosomal DNA (rDNA) and to the recruitment of ribosome biogenesis factors 1–3 . The pre-ribosomal RNA (pre-rRNA) is transcribed by RNA polymerase I (RNAPI) from the rDNA that is arranged in tandem arrays on chromosomes 13, 14, 15, 21, and 22 in human diploid cells 4–6 . A series of endo- and exo- nucleolytic cleavages removes the transcribed spacer sequences from the pre-rRNA to release the mature 18S, 5.8S, and 28S rRNAs 7, 8 .…”

Section: Introductionmentioning

confidence: 99%

Crosstalk between the nucleolus and the DNA damage response

Ogawa

Baserga

2017

Mol. BioSyst.

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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.

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Section: Introductionmentioning

confidence: 99%

Crosstalk between the nucleolus and the DNA damage response

Ogawa

Baserga

2017

Mol. BioSyst.

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“…Light/electronic microscopy, however, reveals that the nucleolus contains three mainly morphologically distinct regions, the fibrillar center (FC), the dense fibrillar component (DFC) and the granular component (GC) [1]. In mammalian cells, several hundred ribosomal DNA genes (rDNA repeats) separated by long intergenic spacers (IGSs) are localized in the FC and are responsible for 47S pre-rRNA transcription [3]. 47S pre-rRNA transcription is dependent on RNA polymerase I (Pol I).…”

Section: Introductionmentioning

confidence: 99%

The roles of RRP15 in nucleolar formation, ribosome biogenesis and checkpoint control in human cells

et al. 2017

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The nucleolus controls ribosome biogenesis and its perturbation induces nucleolar stress that inhibits cell cycle progression and activates checkpoint responses. Here, we investigate the roles of ribosomal RNA processing protein, RRP15, in nucleolar formation, ribosome biogenesis, cell cycle progression and checkpoint control in human cells. RRP15 is localized in the nucleolus and required for nucleolar formation. In contrast to the budding yeast Rrp15p that was reported as a component of pre-60S subunits, RRP15 is found in both pre-40S and pre-60S subunits and involved in regulating rRNA transcription and ribosome biogenesis. Perturbation of RRP15 induces nucleolar stress that activates RPL5/RPL11/5S rRNA (RP)-Mdm2-p53 axis checkpoint response and arrests cells at G1-G1/S in p53-proficient non-transformed RPE1 cells but not in p53-deficient HeLa and MCF7 tumor cells. Instead, p53-deficient HeLa and MCF7 cells with RRP15-dependent nucleolar stress enter S-phase with S-phase perturbation that activates ATR-Chk1- γH2AX axis DNA replication/damage checkpoint response, delaying S-G2/M progression and, ultimately, causing cell death. The selective checkpoint response, cell cycle inhibition and/or cytotoxicity induced by RRP15-dependent nucleolar stress in p53-proficient non-transformed cells and p53-deficient tumor cells suggest that RRP15 might be a potential target for cancer therapy.

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“…Structural and functional aspects of various nuclear components and nuclear bodies were reviewed in the March 2016 special issue of HCB "Focus on: the cell nucleus," among them the nucleolus (Smirnov et al 2016;Weipoltshammer and Schöfer 2016). The nucleolus is the largest nuclear body, and its main function is in ribosome biogenesis.…”

mentioning

confidence: 99%