Department of Cell Biology



Professor, Department of Cell Biology
Chanin Bldg., Room 416

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The Centromere and alpha satellite DNA and the tau protein
Genomic Instability
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    Genomic Instability

Faithful genome replication is essential to maintain normal cell function. Regions that are difficult to replicate can stall replication forks resulting in genomic instability and, threatening genomic integrity. Aberrant replication of any of four fragile regions can result in rearrangements that have pathological consequences. These regions include alpha satellite DNA (located at centromeres), rDNA genes, telomeres and common fragile sites (CFS). One of our overall goals is to elucidate how these distinct classes of biologically important chromosomal fragile sites, are accurately replicated. The knowledge obtained from these studies will provide an essential understanding of how fragile sites are repaired and replicated after DNA damage to prevent genetic dysfunction.

Genomic instability resulting from breakage of DNA or telomere dysfunction is an important contributing factor to cancer, and to congenital and age-related degenerative diseases. A key factor driving this instability is chromosome fusion events, which can lead to rearrangements, deletions or amplifications. Telomere loss and excessive telomere shortening in particular renders telomeres highly susceptible to fusion. By revealing the extent that telomeric initiation protects against telomere loss and chromosomal end fusion, our studies will provide essential mechanistic understanding of replication-dependent telomere maintenance and its contribution to genome stability.