1. A one-day old female newborn was referred to your hospital with complaints of
ID: 260142 • Letter: 1
Question
1. A one-day old female newborn was referred to your hospital with complaints of seizures and multiple congenital abnormalities. You conduct both a physical examination and a laboratory test. Given that you must wait for the laboratory test results, you make a prediction based on the physical examination. You determine that she has Cornelia de Lange syndrome (CdLS). CdLS is a rare genetic disorder associated with mutations affecting the cohesin complex. A) Briefly explain the role of cohesins during the mitotic cell cycle. B) Describe the process that leads to the cleavage of the cohesin complex when there is tension at the kinetochores? Why does cohesin need to be cleaved? What stage of M- phase does this occur? C) Finally, the laboratory results arrive, you make the following observations: 1. There are no mutations associated with the cohesin complex 2. Lower than normal levels of active cdk1/m-cyclin 3. A 2-fold increase in active separase You conclude that the patient doesn't have CdLS. So, you decide to sequence her RNA and discover that she has elevated cdc20 RNA levels. Is this surprising given observation 2 and 3, give an explanation? What therapy would you recommend?Explanation / Answer
Ans A) The cohesin ring performs the following function:
1) It keeps the sister chromatids connected with each other during the metaphase of mitotic cycle. Each sister chromatids segregates to opposite poles. Without the cohesin ring there would be no segregation.
2) It facilitates spindle attachment on chromosomes.
3) Promotes DNA repair by recombination.
4) It has also been found responsible for transcription regulation.
Ans B. Cohesins are removed from chromosome arm by the phosphorylation dependent prophase pathway. Due to chromosome segregation the centrioles loosen their tight orthogonal arrangement, which later licenses centrosome duplication. The cohesin functions as a centriole engagement factor. The ecotopic cleavage is induced by Smc3 which promotes separation of centrioles. Kinetochore microtubule attachment destabilized by the loss of tension caused due to the cleavage of cohesin complex. It occurs during the metaphase anaphase transition.
Ans C. Increased cdc20 levels are associated with the pancreatic ductal adrenocarcinoma differentiation and progression. Studies have revealed that the use of antisense FZR1 RNA injection might inhibit the cdc20 levels.
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