Most immortal human cells maintain their telomeres by up-regulating the enzyme telomerase. Approximately 10-15% of immortal cells maintain their telomere lengths by a recombination-based mechanism termed alternative lengthening of telomeres (ALT). Human ALT cells are characterized by ALT associated promyelocytic bodies (APBs) that contain proteins involved in DNA damage response and repair. Our lab has found significant colocalization of several components of the Fanconi Anemia (FA) pathway with telomeres and demonstrated that knockdown of FANCD2 leads to ALT-specific increase in the amount of telomeric DNA as well as increased aneuploidy and cell death. In this study, we examined the role of FANCM in telomere maintenance in ALT cells. We found a significant colocalization of FANCM with telomeres in two ALT cell lines. Knockdown of FANCM was associated with reduced growth, increases in the size of TRF2 foci and in the amount of telomeric DNA. These data suggest that FANCM plays a role in telomere length regulation and maintenance.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/24237 |
| Date | 05 April 2010 |
| Creators | Al Murshedi, Fathiya |
| Contributors | Meyn, M. Stephen |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
Page generated in 0.0013 seconds