
doi: 10.5772/34114
In all living organisms, cells arise from the division of a pre-existing cell and inherit one copy of the genome identical to that of the mother cell. Any defect in chromosome segregation can lead to aneuploidy via chromosome gain or loss, and consequently to genetic instability, thereby paving the way for malignant growth and cancer. Thus, the faithful distribution of one copy of each chromosome between the two daughter cells is essential to maintain genome stability. Cells have evolved elaborate control mechanisms to ensure that chromosome segregation occurs in an accurate manner. From yeast to human, replicated DNA molecules are held together from their synthesis during S-phase until their separation in mitosis. This sister chromatid cohesion is absolutely essential for faithful transmission of replicated chromosomes during mitosis (for review, see Nasmyth, 2001). Indeed, in early mitosis, cohesion between sister chromatids counteracts the pulling forces exerted by the microtubule filaments emanating from the opposite poles of the mitotic spindle, thereby allowing the proper alignment of chromosomes on the metaphase plate, and their faithful segregation during the subsequent anaphase. In the case of a defective cohesion, the sister chromatids would float around in the cellular space and, as a consequence, would fail to be equally distributed between the two future daughter cells. Cohesion between sister chromatid is not only required for the proper distribution of replicated genomes during mitosis, but is also essential in postreplicative interphase cells for the repair of DNA double-strand breaks by homologous recombination (Sjogren and Nasmyth, 2001)(for review, see Strom and Sjogren, 2007; Watrin and Peters, 2006). The homologous recombination pathway uses an identical copy of the damaged DNA fibre, typically the sister chromatid, as a template to faithfully repair the altered DNA. For the homologous recombination machinery to process chromosome breaks, the broken chromatid and the sister chromatid that is used as a template have to be positioned and maintained in close proximity. It is believed that sister chromatid cohesion provides this spatial proximity between damaged and template chromatids. Consistently, proteins that are required for sister chromatid cohesion are also required for the repair of DNA doublestrand breaks in postreplicative cells (for review, see Watrin and Peters, 2006). Therefore, sister chromatid cohesion plays an essential role in restoring and maintaining the integrity of the genome upon genotoxic stress.
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
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