Correction mechanisms of erroneous kinetochore-microtuble attachments in chromosome segregation

Abstract

During the process of chromosome segregation the duplicated DNA has to be equally segregated between daughter cells. Only then, proper development of daughter cells is possible. Correct chromsome segregation can only be achieved when sister kinetochores are bi-orientated, referring to a state of kinetochore-microtubule attachment where each kinetochore of a pair is attached to a different spindle pole. Because establishment of kinetochore-micorubule attachments is dependent on stochastic events, bi-orientation is not instantly achieved. Sister kinetochores can become attached to the same pole or one kinetochore can bind to microtubules from both spindle poles. These kinetochore orietations will lead to aneuploidy and possibly to the development of cancer. Therefore, establishment of erroneous kinetochore-microtubule attachments has to be prevented in the first instance and corrected if necessary. In this thesis, I will elaborate on the machanisms of prevention and correction of erroneous kinetochore-microtubule attachments and propose a model for correction.