Centrins belong to a family of proteins containing calcium-binding EF-hand motifs that perform well-established roles in centrosome and spindle pole body (SPB) duplication. Yeast encodes a single Centrin protein (Cdc31) that binds components in the SPB. However, further studies revealed a role for Centrins in mRNA export, and interactions with contractile filaments and photoreceptors. In addition, human Centrin-2 can bind the DNA-lesion recognition factor XPC, and improve the efficiency of nucleotide excision repair. Similarly, we reported that yeast Cdc31 binds Rad4, a functional counterpart of the XPC DNA repair protein. We also found that Cdc31 is involved in the ubiquitin/proteasome system, and mutations interfere with intracellular protein turnover. In this report, we describe new findings that indicate a role for Cdc31 in the energy metabolism pathway. Cdc31 and cdc31 mutant proteins showed distinct interactions with proteins in energy metabolism, and mutants showed sensitivity to oxidative stress and poor growth on non-fermentable carbon. Significant alteration in mitochondrial morphology was also detected. Although it is unclear how Cdc31 contributes to so many unrelated mechanisms, we propose that by controlling SPB duplication Centrin proteins might link the cellular responses to DNA damage, oxidative load and proteotoxic stresses to growth control.
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http://dx.doi.org/10.1111/mmi.14128 | DOI Listing |
J Cell Biol
March 2021
Center for Molecular Biology, University of Heidelberg, German Cancer Research Center-Center for Molecular Biology Alliance, Heidelberg, Germany.
The spindle pole body (SPB) provides microtubule-organizing functions in yeast and duplicates exactly once per cell cycle. The first step in SPB duplication is the half-bridge to bridge conversion via the antiparallel dimerization of the centrin (Cdc31)-binding protein Sfi1 in anaphase. The bridge, which is anchored to the old SPB on the proximal end, exposes free Sfi1 N-termini (N-Sfi1) at its distal end.
View Article and Find Full Text PDFSubcell Biochem
February 2020
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge, CB2 0QH, UK.
The Three prime repair exonuclease 2 (TREX-2) complex functions as a platform to which many of the components of the nuclear mRNA processing machinery bind, facilitating integration of this phase of the gene expression pathway, as well as mediating the re-positioning of highly regulated actively transcribing genes (such as GAL1) to nuclear pores (NPCs) to accelerate their activation. In Saccharomyces cerevisiae the TREX-2 complex is based on a Sac3 scaffold to which Thp1, Sem1, Cdc31 and two Sus1 chains are bound. A combination of X-ray crystallography and electron microscopy studies have established the structure of two major regions of this complex: the M-region that functions to bind nucleic acids and the CID region that functions to link the complex to nuclear pores.
View Article and Find Full Text PDFMol Microbiol
December 2018
Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers University, 683 Hoes Lane, SPH-383, Piscataway, NJ, 08854, USA.
Centrins belong to a family of proteins containing calcium-binding EF-hand motifs that perform well-established roles in centrosome and spindle pole body (SPB) duplication. Yeast encodes a single Centrin protein (Cdc31) that binds components in the SPB. However, further studies revealed a role for Centrins in mRNA export, and interactions with contractile filaments and photoreceptors.
View Article and Find Full Text PDFBiol Open
June 2017
Institute for Integrative Biology of the Cell (I2BC), Cell Biology Department, CEA, CNRS, Université Paris Sud, Université Paris-Saclay, 1 Avenue de la Terrasse, Gif sur Yvette 91198, France.
First discovered in unicellular eukaryotes, centrins play crucial roles in basal body duplication and anchoring mechanisms. While the evolutionary status of the founding members of the family, Centrin2/Vfl2 and Centrin3/cdc31 has long been investigated, the evolutionary origin of other members of the family has received less attention. Using a phylogeny of ciliate centrins, we identify two other centrin families, the ciliary centrins and the centrins present in the contractile filaments (ICL centrins).
View Article and Find Full Text PDFNucleic Acids Res
May 2017
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
Transcription-export complex 2 (TREX-2, or THSC) facilitates localization of actively transcribing genes such as GAL1 to the nuclear periphery, contributes to the generation of export-competent mRNPs and influences gene expression through interactions with Mediator. TREX-2 is based on a Sac3 scaffold to which Thp1, Sem1, Cdc31 and Sus1 bind and consists of three modules: the N-region (Sac3∼1-100), which binds mRNA export factor Mex67:Mtr2; the M-region, in which Thp1 and Sem1 bind to Sac3∼100-550; and the CID region in which Cdc31 and two Sus1 chains bind to Sac3∼720-805. Although the M-region of Sac3 was originally thought to encompass residues ∼250-550, we report here the 2.
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