Tension gets chromosomes oriented
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《细胞学杂志》
Mono-oriented chromosomes rapidly reorient (top panels) unless tension is applied with a microneedle (bottom panels).
NICKLAS
By the late 1960s scientists knew that unipolar kinetochore-to-pole attachments are unstable and easily come undone. They also knew that by a somewhat random process, stable bioriented attachments are eventually established. "I had a sequence of pictures of dividing cells on the wall in my office," says Nicklas. "I remember looking at those images and thinking that it would take years to make some sense of ."
But the answer came earlier than expected. A paper by Ronald Dietz first raised the possibility that tension between two kinetochores, generated only in the bioriented state, might discriminate between correct and incorrect attachments (Dietz, 1958). "I thought it was an easy idea to test and that we should do the experiment," says Nicklas. As chance would have it, a recently designed micromanipulator (Ellis, 1962) made the experiment possible. "From a technical point of view, in 1969 this was a very easy experiment to do," says Nicklas. "The challenge was thinking of a way to test the role of tension in chromosome orientation."
Using grasshopper cells in meiosis, Nicklas' group showed that the kinetochore-to-pole connections of chromosomes that were improperly attached could be stabilized by using a glass needle to pull on one of the chromosomes. As a result of the applied tension, the two chromosomes would remain in a unipolar orientation for many hours, and would not achieve the correct orientation. In contrast, in the absence of tension, the same two chromosomes would reorient into the correct configuration within several minutes.
"One problem with our paper was that the act of pulling made the chromosomes point straight to a spindle pole, so that position rather than tension could have been the decisive factor," says Nicklas. To address this point, several years later Nicklas and Ward (1994) were able to repeat the same experiment applying tension in a way that would not affect the position of the chromosomes, thereby confirming that tension was responsible for stabilizing kinetochore-to-pole connections. More current work has shown that the correction of unipolar attachments requires the activity of the Aurora B protein kinase, an enzyme that is highly conserved in yeast and vertebrates (Tanaka et al., 2002; Hauf et al., 2003).
Nicklas's pioneering experiments were conducted in cells undergoing meiosis, so it was not clear whether the same mechanisms would be at play during mitosis. However, recently Dewar et al. (2004) showed that the combination of tension and Aurora B activity is indeed sufficient to ensure that sister chromatids are appropriately aligned during mitosis.
Dewar, H., et al. 2004. Nature. 428:93–97.
Dietz, R. 1958. Chromosoma. 9:359–440.
Ellis, G.W. 1962. Science. 138:84–91.
Hauf, et al. 2003. J. Cell Biol. 161:281–294.
Nicklas, R.B., and C.A. Koch. 1969. J. Cell Biol. 43:40–50.
Nicklas, R.B., and S.C. Ward. 1994. J. Cell Biol. 126:1241–1253.
Tanaka, T.U., et al. 2002. Cell. 108:317–329.(During cell division pairs of chromosome)
NICKLAS
By the late 1960s scientists knew that unipolar kinetochore-to-pole attachments are unstable and easily come undone. They also knew that by a somewhat random process, stable bioriented attachments are eventually established. "I had a sequence of pictures of dividing cells on the wall in my office," says Nicklas. "I remember looking at those images and thinking that it would take years to make some sense of ."
But the answer came earlier than expected. A paper by Ronald Dietz first raised the possibility that tension between two kinetochores, generated only in the bioriented state, might discriminate between correct and incorrect attachments (Dietz, 1958). "I thought it was an easy idea to test and that we should do the experiment," says Nicklas. As chance would have it, a recently designed micromanipulator (Ellis, 1962) made the experiment possible. "From a technical point of view, in 1969 this was a very easy experiment to do," says Nicklas. "The challenge was thinking of a way to test the role of tension in chromosome orientation."
Using grasshopper cells in meiosis, Nicklas' group showed that the kinetochore-to-pole connections of chromosomes that were improperly attached could be stabilized by using a glass needle to pull on one of the chromosomes. As a result of the applied tension, the two chromosomes would remain in a unipolar orientation for many hours, and would not achieve the correct orientation. In contrast, in the absence of tension, the same two chromosomes would reorient into the correct configuration within several minutes.
"One problem with our paper was that the act of pulling made the chromosomes point straight to a spindle pole, so that position rather than tension could have been the decisive factor," says Nicklas. To address this point, several years later Nicklas and Ward (1994) were able to repeat the same experiment applying tension in a way that would not affect the position of the chromosomes, thereby confirming that tension was responsible for stabilizing kinetochore-to-pole connections. More current work has shown that the correction of unipolar attachments requires the activity of the Aurora B protein kinase, an enzyme that is highly conserved in yeast and vertebrates (Tanaka et al., 2002; Hauf et al., 2003).
Nicklas's pioneering experiments were conducted in cells undergoing meiosis, so it was not clear whether the same mechanisms would be at play during mitosis. However, recently Dewar et al. (2004) showed that the combination of tension and Aurora B activity is indeed sufficient to ensure that sister chromatids are appropriately aligned during mitosis.
Dewar, H., et al. 2004. Nature. 428:93–97.
Dietz, R. 1958. Chromosoma. 9:359–440.
Ellis, G.W. 1962. Science. 138:84–91.
Hauf, et al. 2003. J. Cell Biol. 161:281–294.
Nicklas, R.B., and C.A. Koch. 1969. J. Cell Biol. 43:40–50.
Nicklas, R.B., and S.C. Ward. 1994. J. Cell Biol. 126:1241–1253.
Tanaka, T.U., et al. 2002. Cell. 108:317–329.(During cell division pairs of chromosome)