Overlapping roles of the spindle assembly and DNA damage checkpoints in the cell-cycle response to altered chromosomes in Saccharomyces cerevisiae.
Overlapping roles of the spindle assembly and DNA damage checkpoints in the cell-cycle response to altered chromosomes in Saccharomyces cerevisiae.
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作者：
P. M. Garber;J. Rine
mad2依赖性纺锤体检查点阻断后期，直到所有染色体成功地与有丝分裂纺锤体实现双极性附着。DNA损伤和DNA复制检查点阻断了DNA损伤的后期反应，可能包括单链DNA和停滞的复制分叉。许多激活DNA损伤和DNA复制检查点的相同条件也激活了纺锤体检查点。mad2Delta突变部分缓解了细胞对影响复制蛋白Mcm3p和Pol1p突变的抑制反应。因此，纺锤体检查点功能的一个以前未被认识的方面可能是保护细胞免受DNA复制缺陷的影响。此外，在缺乏DNA损伤或DNA复制检查点的细胞中，纺锤体检查点有助于细胞对DNA损伤剂甲磺酸甲酯、复制抑制剂羟基脲以及影响Mcm2p和Orc2p的突变的抑制反应。因此纺锤体检查点对更大范围的染色体扰动比以前认识到的敏感。最后，当ORC、Mcm蛋白或DNA聚合酶δ发生突变时，DNA复制检查点对细胞的阻滞没有贡献。因此，这种检查点的特异性可能比以前认识到的更有限。
The MAD2-dependent spindle checkpoint blocks anaphase until all chromosomes have achieved successful bipolar attachment to the mitotic spindle. The DNA damage and DNA replication checkpoints block anaphase in response to DNA lesions that may include single-stranded DNA and stalled replication forks. Many of the same conditions that activate the DNA damage and DNA replication checkpoints also activated the spindle checkpoint. The mad2Delta mutation partially relieved the arrest responses of cells to mutations affecting the replication proteins Mcm3p and Pol1p. Thus a previously unrecognized aspect of spindle checkpoint function may be to protect cells from defects in DNA replication. Furthermore, in cells lacking either the DNA damage or the DNA replication checkpoints, the spindle checkpoint contributed to the arrest responses of cells to the DNA-damaging agent methyl methanesulfonate, the replication inhibitor hydroxyurea, and mutations affecting Mcm2p and Orc2p. Thus the spindle checkpoint was sensitive to a wider range of chromosomal perturbations than previously recognized. Finally, the DNA replication checkpoint did not contribute to the arrests of cells in response to mutations affecting ORC, Mcm proteins, or DNA polymerase delta. Thus the specificity of this checkpoint may be more limited than previously recognized.