Nejvíce citovaný článek - PubMed ID 11509732
Receiving complete and undamaged genetic information is vital for the survival of daughter cells after chromosome segregation. The most critical steps in this process are accurate DNA replication during S phase and a faithful chromosome segregation during anaphase. Any errors in DNA replication or chromosome segregation have dire consequences, since cells arising after division might have either changed or incomplete genetic information. Accurate chromosome segregation during anaphase requires a protein complex called cohesin, which holds together sister chromatids. This complex unifies sister chromatids from their synthesis during S phase, until separation in anaphase. Upon entry into mitosis, the spindle apparatus is assembled, which eventually engages kinetochores of all chromosomes. Additionally, when kinetochores of sister chromatids assume amphitelic attachment to the spindle microtubules, cells are finally ready for the separation of sister chromatids. This is achieved by the enzymatic cleavage of cohesin subunits Scc1 or Rec8 by an enzyme called Separase. After cohesin cleavage, sister chromatids remain attached to the spindle apparatus and their poleward movement on the spindle is initiated. The removal of cohesion between sister chromatids is an irreversible step and therefore it must be synchronized with assembly of the spindle apparatus, since precocious separation of sister chromatids might lead into aneuploidy and tumorigenesis. In this review, we focus on recent discoveries concerning the regulation of Separase activity during the cell cycle.
- Klíčová slova
- CDK1, Cyclin B1, Mad2, Sgo2, aneuploidy, chromosome division, cohesin, securin, segregation errors, separase,
- MeSH
- anafáze * MeSH
- aparát dělícího vřeténka metabolismus MeSH
- chromatidy * metabolismus MeSH
- mitóza MeSH
- proteiny buněčného cyklu metabolismus MeSH
- segregace chromozomů MeSH
- separáza genetika metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- proteiny buněčného cyklu MeSH
- separáza MeSH
According to a general paradigm, proper DNA duplication from each replication origin is ensured by two protein complexes termed replisomes. In prokaryotes and in budding yeast Saccharomyces cerevisiae, these two replisomes seem to be associated with one another until DNA replication initiated from the origin has finished. This arrangement results in the formation of the loop of newly synthesized DNA. However, arrangement of replisomes in other eukaryotic organisms including vertebrate cells is largely unknown. Here, we used in vivo labeling of DNA segments in combination with the electron microscopy tomography to describe the organization of replisomes in human HeLa cells. The experiments were devised in order to distinguish between a model of independent replisomes and a model of replisome couples. The comparative analysis of short segments of replicons labeled in pulse-chase experiments of various length shows that replisomes in HeLa cells are organized into the couples during DNA replication. Moreover, our data enabled to suggest a new model of the organization of replicated DNA. According to this model, replisome couples produce loop with the associated arms in the form of four tightly associated 30nm fibers.
- MeSH
- bromodeoxyuridin metabolismus MeSH
- buněčné jádro metabolismus ultrastruktura MeSH
- chromatin fyziologie ultrastruktura MeSH
- deoxyuracilnukleotidy metabolismus MeSH
- DNA-dependentní DNA-polymerasy chemie metabolismus MeSH
- HeLa buňky MeSH
- konformace nukleové kyseliny MeSH
- lidé MeSH
- modely genetické * MeSH
- multienzymové komplexy chemie metabolismus MeSH
- počítačové zpracování obrazu MeSH
- replikace DNA fyziologie MeSH
- replikon genetika MeSH
- tomografie elektronová MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- bromodeoxyuridin MeSH
- chromatin MeSH
- deoxyuracilnukleotidy MeSH
- DNA synthesome MeSH Prohlížeč
- DNA-dependentní DNA-polymerasy MeSH
- multienzymové komplexy MeSH