Beyond the code: the mechanical properties of DNA as they relate to mitosis

Bloom, Kerry

doi:10.1007/s00412-007-0138-0

Cited by 70 publications

(59 citation statements)

References 40 publications

(54 reference statements)

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“…In vitro, LIS1 significantly improves the processivity of dynein under a heavy load (McKenney et al, 2010). Our results are consistent with this idea and suggest that, in fungal hyphae, with viscosity and cytoplasmic streaming towards the hyphal tip (Bloom, 2008;Lang et al, 2010), early endosomes are heavy enough loads to make NUDF necessary for dynein to carry them along microtubules.…”

Section: Dynein Colocalizes With Abnormally Accumulated Early Endosomsupporting

confidence: 87%

The microtubule plus-end localization ofAspergillusdynein is important for dynein–early-endosome interaction but not for dynein ATPase activation

Zhang

Zhuang

Lee

et al. 2010

Journal of Cell Science

109

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Cytoplasmic dynein is a multi-subunit microtubule motor that uses the ATPase activity of its heavy chain to move towards the minus-end of a microtubule. In vivo, cytoplasmic dynein is important for the positioning of nuclei and spindles and the retrograde transport of vesicles, signaling molecules and viruses (Karki and Holzbaur, 1999;Schroer, 2004;Soldati and Schliwa, 2006;Greber and Way, 2006;Abe and Cavalli, 2008). Interestingly, although cytoplasmic dynein is a minus-enddirected motor, it accumulates at the microtubule plus-end in many cell types (Vaughan et al., 1999;Han et al., 2001;Ma and Chisholm, 2002;Lee et al., 2003;Sheeman et al., 2003;Lenz et al., 2006;Vogel et al., 2009). This accumulation at the microtubule plus-end is important for a variety of functions. For example, it might facilitate interaction with cortical proteins for spindle positioning Sheeman et al., 2003;Markus et al., 2009). In addition, because vesicles that need to undergo retrograde transport often start their journey at the plusend, the accumulation of dynein at the plus-end is thought to facilitate loading of membranous cargoes (Vaughan et al., 2002;Lenz et al., 2006).It has been found in several fungal organisms including Aspergillus nidulans, Saccharomyces cerevisiae and Ustilago maydis that the accumulation of dynein at the microtubule plusend depends on plus-end-directed kinesins (Zhang et al., 2003;Carvalho et al., 2004;Lenz et al., 2006;Caudron et al., 2008). In filamentous fungi and in neurons, kinesin 1 is important for plusend accumulation of dyenin (Zhang et al., 2003;Lenz et al., 2006;Yamada et al., 2009) and, importantly, as first discovered in U. maydis, dynein-mediated retrograde movement of early endosomes also depends on the function of kinesin 1 (Lenz et al., 2006;Abenza et al., 2009;Zekert and Fischer, 2009). These results strongly support the notion that plus-end accumulation of dynein is important for its function in vesicle trafficking. In filamentous fungi, the dynactin complex (Schroer, 2004) as well as several dynein subunits are also important for the accumulation of dynein at the microtubule plus-end (Zhang et al., 2002;Zhang et al., 2003;Zhang et al., 2008;Zhang et al., 2009;Liu et al., 2003;Lenz et al., 2006).Whether and how dynein activity is regulated at the plus-end remain to be addressed. It is thought that dynein must remain inactive at the plus-end until it interacts with cargo and/or other protein factors Sheeman et al., 2003;Zhang et al., 2003;Lenz et al., 2006;Steinberg, 2007). However, it is unclear whether dynein only gets activated at the plus-end or if it is already active before arriving at the plus-end. Here, we tested in A. nidulans whether dynein is an active ATPase before it arrives at the plus-end and whether plus-end localization is a prerequisite for activating the dynein ATPase. Our results suggest that dynein is an active ATPase before it arrives at the plus-end. The kinesin-1-mediated accumulation of dynein at the plus-ends might facilitate the interaction between early endosom...

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Section: Dynein Colocalizes With Abnormally Accumulated Early Endosomsupporting

confidence: 87%

The microtubule plus-end localization ofAspergillusdynein is important for dynein–early-endosome interaction but not for dynein ATPase activation

Zhang

Zhuang

Lee

et al. 2010

Journal of Cell Science

109

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“…Thus, our current result provides a strong support for the idea that besides its binding to other subunits, the tail is important for regulating dynein motor function in vivo. It is worth pointing out that in vivo, the dynein motor carrying a cargo not only needs to move in a cytoplasm with considerable viscosity (63,64) but also needs to compete with plus-end-directed motors bound to the same cargo (65)(66)(67). In filamentous fungi, kinesin-3 is able to bind to the dynein-bound early endosome and be carried to the minus end as a cargo of dynein (40,53,68).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Site in the Tail of Dynein Heavy Chain Important for Dynein Function in Vivo

Qiu

Zhang

Xiang

2013

Journal of Biological Chemistry

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Background:The dynein heavy chain tail is required for subunit interactions but not for in vitro motility. Results: A dynein tail mutation affects dynein function in vivo without affecting subunit interactions. Conclusion: A site upstream of the subunit interaction sites of the dynein tail is important in vivo. Significance: This study discovers a novel site of the dynein tail critical for motor function in vivo.

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“…In contrast, mec1 sml1 cells are largely proficient for bipolar attachment but experience lethal chromosome breaks due to nondisjunction of incompletely replicated chromosomes. Although the force exerted by a spindle microtubule Bloom 2008) is thought to be insufficient to make a dsDNA break (Bensimon et al 1995), the presence of ssDNA brings spindle force-induced breakage into the realm of possibility. Alternatively, spindle force may induce chromatin unraveling, making regions more accessible to nucleases-an idea consistent with our observation of discrete breakage sites ( Figure 4D; see File S1 for a fuller discussion).…”

Section: Discussionmentioning

confidence: 99%

“…Phys Rev Lett 74, 4754-4757. Bloom, K. S. (2008). Beyond the code: the mechanical properties of DNA as they relate to mitosis.…”

Section: Supplemental Discussionmentioning

confidence: 99%

“…Based on previous calculations of maximum force on a yeast kinetochore microtubule-47 pN (piconewton) measured in the grasshopper spermatocytes and 10 pN in budding yeast (Bloom, 2008)-it is unlikely that the force from a pair of microtubules per yeast chromosome (10 pN x 2 microtubules = 20 pN) is enough to break the chromosome, which requires a calculated force of 480 pN (+/-20%) (Bensimon et al, 1995). However, the estimated force for chromosome breakage was calculated for the breaking of double-stranded DNA (Jannink et al, 1996).…”

Section: Supplemental Discussionmentioning

confidence: 99%

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Centromere Replication Timing Determines Different Forms of Genomic Instability inSaccharomyces cerevisiaeCheckpoint Mutants During Replication Stress

Feng¹,

Bachant

Collingwood

et al. 2009

Genetics

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Yeast replication checkpoint mutants lose viability following transient exposure to hydroxyurea, a replication-impeding drug. In an effort to understand the basis for this lethality, we discovered that different events are responsible for inviability in checkpoint-deficient cells harboring mutations in the mec1 and rad53 genes. By monitoring genomewide replication dynamics of cells exposed to hydroxyurea, we show that cells with a checkpoint deficient allele of RAD53, rad53K227A, fail to duplicate centromeres. Following removal of the drug, however, rad53K227A cells recover substantial DNA replication, including replication through centromeres. Despite this recovery, the rad53K227A mutant fails to achieve biorientation of sister centromeres during recovery from hydroxyurea, leading to secondary activation of the spindle assembly checkpoint (SAC), aneuploidy, and lethal chromosome segregation errors. We demonstrate that cell lethality from this segregation defect could be partially remedied by reinforcing bipolar attachment. In contrast, cells with the mec1-1 sml1-1 mutations suffer from severely impaired replication resumption upon removal of hydroxyurea. mec1-1 sml1-1 cells can, however, duplicate at least some of their centromeres and achieve bipolar attachment, leading to abortive segregation and fragmentation of incompletely replicated chromosomes. Our results highlight the importance of replicating yeast centromeres early and reveal different mechanisms of cell death due to differences in replication fork progression.

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Beyond the code: the mechanical properties of DNA as they relate to mitosis

Cited by 70 publications

References 40 publications

The microtubule plus-end localization ofAspergillusdynein is important for dynein–early-endosome interaction but not for dynein ATPase activation

The microtubule plus-end localization ofAspergillusdynein is important for dynein–early-endosome interaction but not for dynein ATPase activation

Identification of a Novel Site in the Tail of Dynein Heavy Chain Important for Dynein Function in Vivo

Centromere Replication Timing Determines Different Forms of Genomic Instability inSaccharomyces cerevisiaeCheckpoint Mutants During Replication Stress

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