Preventing aneuploidy and the consequences of failure

The maintenance and transmission of genetic material is critical for the survival of cells and organisms. Sexually reproducing diploid organisms undergo meiosis to produce haploid gametes, so that the resulting progeny are diploid. During meiosis I homologous chromosomes segregate to opposite poles, whereas sister chromatids segregate in meiosis II. A failure to segregate chromosomes correctly in either division results in offspring having an incorrect chromosome number: a condition called aneuploidy. Aneuploidy has been associated with several developmental defects and is a hallmark of cancer. Meiotic segregation errors are quite frequent in humans and are responsible for the 'maternal age effect.' This thesis addresses both the causes and consequences of aneuploidy. We first investigate the mechanisms that ensure faithful segregation of chromosomes during meiosis in the budding yeast Saccharomyces cerevisiae. The conserved Aurora B kinase is found to be responsible for detecting, and attempting to correct, incorrect kinetochore-microtubule attachments during both meiotic divisions. The meiosis I-specific protein Maml is found to link sister chromatids in a cohesin-independent manner, ensuring that they segregate together in meiosis I. In the presence of Maml, Aurora B can distinguish between sister chromatids and homologous chromosomes. Thus, Maml allows Aurora B to perform similar functions in both meiotic divisions, yet with profoundly different effects.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2009

Author dc:creator

• Prabhu, Vineet R. (Vineet Ranjan)

Advisor dc:contributor.advisor

• Angelika Amon.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/47882

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/47882