KinetochoreReview2004 - Commentary 5461 The dynamic...

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Introduction The remarkable movements of chromosomes in mitosis are initiated, controlled and monitored by kinetochores, which are structures that form the interface between the chromosomes and the microtubules of the mitotic spindle. Kinetochores of animal cells can be subdivided into two regions. The inner kinetochore normally forms on highly repetitive DNA sequences and assembles into a specialized form of chromatin that persists throughout the cell cycle. The outer kinetochore is a proteinaceous structure with many dynamic components that assembles and functions only during mitosis. Kinetochore functions include attachment of chromosomes to the spindle microtubules, monitoring those attachments, activating a signalling (checkpoint) pathway to delay cell-cycle progression if defects are detected and helping to power the movements of chromosomes on the spindle. We begin by discussing the molecular organization and assembly pathway of the kinetochore. Microtubules are metastable polymers of α - and β -tubulin that switch between phases of growth and shrinkage, a phenomenon known as ‘dynamic instability’ (Mitchison and Kirschner, 1984). We discuss below how the highly dynamic nature of microtubule behaviour is integrated with kinetochore function to move and segregate chromosomes. More details about spindle checkpoint function, spindle assembly mechanisms and the dynamics and mechanics of the microtubule plus end are reviewed elsewhere (Musacchio and Hardwick, 2002; Sharp et al., 2000; Compton, 2000; Kapoor and Compton, 2002; Howard and Hyman, 2003). Here we focus on the animal kinetochore and in particular the interface between the outer kinetochore domain and spindle microtubules (for reviews, see Fukagawa, 2004; Amor et al., 2004). [For reviews of budding and fission yeast kinetochores and plant kinetochores, see Yu et al. and others (Yu et al., 2000; Kitagawa and Hieter, 2001; Cheeseman et al., 2002b; Biggins and Walczak, 2003; McAinsh et al., 2003; Cleveland et al., 2003; Westermann et al., 2003; Houben and Schubert, 2003; Hall et al., 2004).] Animal kinetochore structure The kinetochore (Fig. 1) is composed of several distinct layers that were first observed by conventional fixation and staining methods for electron microscopy (Brinkley and Stubblefield, 1966; Jokelainen, 1967; Comings and Okada, 1971) (reviewed by Rieder, 1982), and more recently by fast freezing/freeze substitution (McEwen et al., 1998). Innermost is an inner plate, a chromatin structure containing nucleosomes with at least one specialized histone, auxiliary proteins and DNA. The makeup and organization of this DNA remains one of the least understood aspects of the kinetochore in animal cells. The inner plate exists as a discrete heterochromatin domain throughout the cell cycle. Outside this is an outer plate composed primarily, if not solely, of protein (Cooke et al., 1993). This structure forms on the surface of the chromosome 5461 The kinetochore is a control module that both powers and regulates chromosome segregation in mitosis and meiosis.
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This note was uploaded on 09/06/2008 for the course BIOMEDE 418 taught by Professor Hunt during the Winter '08 term at University of Michigan.

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KinetochoreReview2004 - Commentary 5461 The dynamic...

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