During which phase are the sister chromatids pulled to opposite ends of the cell?
Securin can act as an oncogene in cultured cells and is overexpressed in some human pituitary tumors. Overexpression of securin may disrupt the timing of chromosome segregation, leading to chromosome loss and, ultimately, contributing to cancer progression. View chapterPurchase book Read full chapter URL: https://www.sciencedirect.com/science/article/pii/B978032334126400044X G2 Phase, Responses to DNA Damage, and Control of Entry Into MitosisIn Cell Biology (Third Edition), 2017 G2/M CheckpointSeparation of sister chromatids during mitosis is a potential danger point for a cell. After DNA is replicated each chromosome consists of paired sister chromatids held together by cohesin. Therefore, if the DNA is damaged, the cell can use information present in the undamaged chromatid to guide the repair process. However, once sisters separate, this corrective mechanism can no longer operate. In addition, if a cell enters mitosis before completing replication of its chromosomes, attempts to separate sister chromatids damage the chromosomes. To minimize these hazards, a checkpoint operates in the G2 phase to block mitotic entry if DNA is damaged or DNA replication is incomplete. Just as DNA damage can arrest the cell cycle in G1 phase, damaged or unreplicated DNA also halts the cell cycle temporarily in the G2 phase. Interestingly, the G1 checkpoint—which can be activated by a single DNA break in human cells—is more sensitive than the G2/M checkpoint, which requires 10 to 20 breaks to block cell-cycle progression. The G2/M checkpoint may be less sensitive then the G1 checkpoint, because G2 cells are already primed to enter mitosis. Consequently, human cells can enter mitosis with limited amounts of damaged or unreplicated DNA. These problem regions can be detected and repaired in the daughter cells after division (see later). Studies of radiation-induced G2 delay in budding yeast identified a major cell-cycle checkpoint that is sensitive to the status of the cellular DNA. Cells defective in this checkpoint are more sensitive than wild-type cells to radiation injury because they continue to divide, despite the presence of broken or otherwise damaged chromosomes (Fig. 43.8). The cells die, presumably from chromosomal defects or loss. In metazoans, the G2/M checkpoint delays entry into mitosis until the damage is either fixed, triggers cell suicide by apoptosis, or causes cells to enter a nonproliferating (senescent) state. The checkpoint works by modulating the activities of the components that control the G2/M transition. View chapterPurchase book Read full chapter URL: https://www.sciencedirect.com/science/article/pii/B9780323341264000438 MitosisP. Wadsworth, J. Titus, in Encyclopedia of Biological Chemistry (Second Edition), 2013 AnaphaseDuring anaphase, sister chromatids separate and move to the spindle poles (Figures 2 and 3). Anaphase consists of two phases, anaphase A and B. During anaphase A, the chromosomes move to the poles and kinetochore fiber microtubules shorten; during anaphase B, the spindle poles move apart as interpolar microtubules elongate and slide past one another. Many cells undergo both anaphase A and B motions, but, in some cases, one or the other motion dominates. Separation of the paired sister chromatids is required for poleward motion in anaphase. Chromatid separation results from the proteolytic degradation of components that link the chromatids at the centromere. Degradation is triggered by the activity of the anaphase-promoting complex, which regulates cell-cycle progression. Chromatid separation is not the result of tugging by microtubules and motor proteins, and can be observed even in the absence of microtubules. Although the motion of the chromosomes to the spindle poles in anaphase has fascinated biologists for many years, the molecular basis for this motion remains controversial and incompletely understood. During anaphase A, kinetochore microtubules must shorten as the chromosomes move poleward. Measurements of spindle flux show that subunit loss from microtubules occurs at the spindle poles during anaphase. In many cells, however, the rate that chromosomes move exceeds the rate of subunit loss at the pole, and, thus, subunit loss must also occur at the kinetochore. Pioneering studies of mitosis in living embryonic cells demonstrated that assembly and disassembly of microtubule polymers result in chromosome motion. This work led to the hypothesis that microtubule disassembly drives chromosome motion. Later work identified molecular motors at the kinetochore, leading to the alternative hypothesis that forces generated by molecular motors drive chromosome motion. One possibility is that molecular motors power chromosome motion, but kinetochore microtubule disassembly limits the rate of chromosome motion. Alternatively, disassembly may be responsible for chromosome motion, and motors may tether the chromosomes to the shortening fiber. The presence of potentially redundant mechanisms for chromosome motion may reflect the fact that mitotic fidelity is of utmost importance. |