Telomere biology and immune system.
Extract: In the 1960s Hayflick reported that normal human somatic cells have a finite replicative capacity and that, after a limited number of cell divisions, cells no longer divide and enter a state termed senescence. Since this observation was made, considerable research energy has focused on identifying molecular pathways that regulate the proliferative capacity of normal somatic (body) cells. One molecular mechanism that has been implicated in the regulation of somatic cell proliferation is mediated by telomeres -- specialized DNA-protein structures that cap the ends of all linear chromosomes. In mammalian cells, telomeres are composed of hexanucleotide repeats (TTAGGG) and a variety of associated proteins. Although all mammalian telomeres are composed of these (TTAGGG) repeats, telomere length varies substantially between different species. The higher order chromatin structure formed by telomeres functions to protect chromosomes ends from degradation and activation of DNA-repair pathways. In the absence of compensatory mechanisms, telomeres shorten progressively with successive rounds of cell division as a result of incomplete replication of telomeric termini, until they reach a critically short length that is no longer protective. Cells that lack protective telomeres fail to proliferate, and they undergo senescence or apoptosis.
Hathcock
Karen S
KS
Experimental Immunology Branch, National Cancer Institute, 10 Center Drive, Bethesda, MD 20892, USA.
Chiang
Y Jeffrey
YJ
Hodes
Richard J
RJ