Human common fragile sites, identification, and analysis of breaks using <i>saccharomyces cerevisiae</i>

<p>Common fragile sites, which are areas of the genome prone to breaks under replication stress, are frequently altered in tumor cells. Two hypotheses have been proposed to explain why common fragile sites break: (1)AT-rich segments with high flexibility in the fragile site fold into secondary structures, leading to replication fork stalling and chromosomal breakage, and (2) Fragile site regions lack sufficient origins of replication, which paired with replication stress results in failure to complete replication before mitosis and eventual breakage of unreplicated DNA. To test these hypotheses, we mapped 30 break locations in each of two yeast artificial chromosomes (YACs) containing human DNA inserts from fragile sites FRA3B and FRA7H. We compared break locations with the locations of high flexibility regions and potential origins. Breaks in both FRA3B and FRA7H are located far from potential origins. These data support the second hypothesis. Breaks in FRA3B, but not FRA7H, are located near high flexibility regions. Thus, secondary structure formation may contribute to breakage in FRA3B but is unlikely to contribute to breakage in FRA7H.</p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Open Access Thesis

Discipline thesis:degree_discipline

Biology

Year dc:date.available

2013

Author dc:creator

• Fitzsimmons, William Joseph

Contributors dc:contributor

• Dr. Anne Casper, Ph.D, Chair
• Dr. Bob Winning, Ph.D
• Dr. David Kass, Ph.D

• DNA
• chromosomes
• cells
• Biology

Repository record dc:identifier

https://commons.emich.edu/theses/501

OAI identifier oai:identifier

oai:commons.emich.edu:theses-1872