CENP-A and topoisomerase-II antagonistically affect chromosome length
| Autor: | Tanner C Fadero, Jennifer K. Heppert, Amy Shaub Maddox, Rajesh Ranjan, Lydia Smith, Bob Goldstein, Paul S. Maddox, Anne Marie Ladouceur |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Chromosomal Proteins Non-Histone Mitosis macromolecular substances Biology Autoantigens Eukaryotic chromosome structure Chromosomes 03 medical and health sciences Report Centromere Animals Caenorhabditis elegans Caenorhabditis elegans Proteins Kinetochores Research Articles Kinetochore Gene Expression Regulation Developmental Chromosome Cell Biology Chromatin Assembly and Disassembly Molecular biology Chromatin 3. Good health DNA Topoisomerases Type II 030104 developmental biology Premature chromosome condensation RNA Interference Centromere Protein A Satellite chromosome |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.201608084 |
| Popis: | The size of mitotic chromosomes is coordinated with cell size. Through an RNAi screen in Caenorhabditis elegans, Ladouceur et al. identify CENP-A and topo-II as factors affecting chromosome length. Quantitative analyses of protein dynamics suggest that CENP-A and topo-II localize and function independently to provide centromeric chromatin structure and determine the length of holocentric mitotic chromosomes. The size of mitotic chromosomes is coordinated with cell size in a manner dependent on nuclear trafficking. In this study, we conducted an RNA interference screen of the Caenorhabditis elegans nucleome in a strain carrying an exceptionally long chromosome and identified the centromere-specific histone H3 variant CENP-A and the DNA decatenizing enzyme topoisomerase-II (topo-II) as candidate modulators of chromosome size. In the holocentric organism C. elegans, CENP-A is positioned periodically along the entire length of chromosomes, and in mitosis, these genomic regions come together linearly to form the base of kinetochores. We show that CENP-A protein levels decreased through development coinciding with chromosome-size scaling. Partial loss of CENP-A protein resulted in shorter mitotic chromosomes, consistent with a role in setting chromosome length. Conversely, topo-II levels were unchanged through early development, and partial topo-II depletion led to longer chromosomes. Topo-II localized to the perimeter of mitotic chromosomes, excluded from the centromere regions, and depletion of topo-II did not change CENP-A levels. We propose that self-assembly of centromeric chromatin into an extended linear array promotes elongation of the chromosome, whereas topo-II promotes chromosome-length shortening. |
| Databáze: | OpenAIRE |
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