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The role of fission yeast nuclear actin-related protein in mitosis.

Minoda, A.; (2005) The role of fission yeast nuclear actin-related protein in mitosis. Doctoral thesis , University of London. Green open access

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Abstract

Nuclear actin-related proteins (Arps) have 20-30% identity to conventional actin and many are found to be in chromatin remodelling complexes. There are two families of chromatin remodelling complexes, one of which carries out covalent modification on histones such as acetylation. The other is an ATPase complex, which alters the nucleosomal spacing, and nuclear Arps are found in both complexes. These complexes are believed to be required for transcriptional activation by increasing the accessibility of the transcription machinery to the target DNA. The alp5-1134 mutant was isolated from a screen for temperature-sensitive (ts) mutants with altered polarity and shows severe mitotic defects. Cloning of alp5+ revealed that Alp5 is an essential actin-related protein, most similar to budding yeast Arp4 and human BAF53. Alp5 localises to the nucleus and immunoprecipitates with Mst1, a histone acetyltransferase. These results strongly indicate the role of Alp5 in chromatin remodelling process, as its homologues. Given the interaction between Alp5 and Mst1, its function in histone acetylation was investigated both genetically and biochemically. It was found that Alp5 is required for acetylating the N-terminus tail of histone H4 lysine residues, and functionally counteracts with the histone deacetylases Clr6, Hst4 and Sir2. At the restrictive temperature, the alp5-1134 mutant shows a mitotic delay due to the activation of a spindle assembly checkpoint, which suggests a defect in the kinetochore-spindle interaction. This study also reveals that the function of Alp5 is required for the transcriptional repression at the core centromere region. Possible roles of Alp5 in mitosis are discussed.

Type: Thesis (Doctoral)
Title: The role of fission yeast nuclear actin-related protein in mitosis.
Identifier: PQ ETD:592157
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest. Third party copyright material has been removed from the ethesis
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: http://discovery.ucl.ac.uk/id/eprint/1444847
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