| The telomere is a chromosomal structure important for the maintenance of genome stability, thereby contributing to the control of cellular proliferation and senescence. Telomere length is regulated by the enzyme telomerase. Under normal circumstances, in the absence of telomerase activity, telomere shortening serves as a mitotic clock. Telomere lengths vary both within and among vertebrates, in general ranging from 10 to 25 Kb. However, the chicken genome has telomere lengths ranging from 10 Kb to 4 Mb at the termini of chromosomes, including a special class of telomeres termed mega-telomeres (100 Kb to 4 Mb). Mega-telomeres are present in all chicken genetic lines studied to date; however, the location and number vary among lines. Cells of the immortalized telomerase-negative chicken cell line, DF-1, possesses a large amount of telomeric DNA, over 3-fold more than normal chicken cells. In abnormal states, some immortalized human cells (including tumors) are telomerase-negative; these cells maintain their telomeres by a pathway termed alternative lengthening of telomeres (ALT). Although the mechanistic details have not been determined, the pathway appears to use recombination of telomeres and markers exist to determine the presence of this pathway. In this dissertation research, telomere length variation and maintenance mechanisms were investigated in chicken cells. Chapter One reviews the literature for telomere biology, telomerase, and ALT. Chapter Two describes the variation of telomeric arrays, including mega-telomeres within and among chicken genetic lines and specialized cell lines. Chapter Three presents an analysis of telomere maintenance mechanisms, including telomerase and ALT, within chicken cell lines. |
