Characterization of HCP-6, a C. elegans protein required to prevent chromosome twisting and merotelic attachment.
Previous studies of mitosis show that capture of single kinetochores by microtubules from both centrosomes (merotelic orientation) is a major cause of aneuploidy. We have characterized hcp-6, a temperature-sensitive chromosome segregation mutant in C. elegans that exhibits chromosomes attached to both poles via a single sister kinetochore. We demonstrate that the primary defect in this mutant is a failure to fully condense chromosomes during prophase. Although centromere formation and sister centromere resolution remain unaffected in hcp-6, the chromosomes lack the rigidity of wild-type chromosomes and twist around the long axis of the chromosome. As such, they are unable to establish a proper orientation at prometaphase, allowing individual kinetochores to be captured by microtubules from both poles. We therefore propose that chromosome rigidity plays an essential role in maintaining chromosome orientation to prevent merotelic capture.
Stear
Jeffrey H
JH
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Roth
Mark B
MB
D000595:Amino Acid Sequence; D000705:Anaphase; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000502:physiology*; D002503:Centromere / Q000378:metabolism; D002875:Chromosomes / Q000378:metabolism*; D018244:Chromosomes, Artificial, Yeast; D003001:Cloning, Molecular; D049452:Green Fluorescent Proteins; D018386:Kinetochores / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008938:Mitosis; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011418:Prophase; D012329:RNA, Bacterial; D012854:Sister Chromatid Exchange; D013696:Temperature
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; C459882:HCP-6 protein, C elegans; D008164:Luminescent Proteins; C042027:RNA I; D012329:RNA, Bacterial; D049452:Green Fluorescent Proteins