Meier Bettina, Clejan Iuval, Liu Yan, Lowden Mia, Gartner Anton, Hodgkin Jonathan, Ahmed Shawn
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.
PLoS Genet. 2006 Feb;2(2):e18. doi: 10.1371/journal.pgen.0020018. Epub 2006 Feb 10.
Mutants of trt-1, the Caenorhabditis elegans telomerase reverse transcriptase, reproduce normally for several generations but eventually become sterile as a consequence of telomere erosion and end-to-end chromosome fusions. Telomere erosion and uncapping do not cause an increase in apoptosis in the germlines of trt-1 mutants. Instead, late-generation trt-1 mutants display chromosome segregation defects that are likely to be the direct cause of sterility. trt-1 functions in the same telomere replication pathway as mrt-2, a component of the Rad9/Rad1/Hus1 (9-1-1) proliferating cell nuclear antigen-like sliding clamp. Thus, the 9-1-1 complex may be required for telomerase to act at chromosome ends in C. elegans. Although telomere erosion limits replicative life span in human somatic cells, neither trt-1 nor telomere shortening affects postmitotic aging in C. elegans. These findings illustrate effects of telomere dysfunction in C. elegans mutants lacking the catalytic subunit of telomerase, trt-1.
秀丽隐杆线虫端粒酶逆转录酶trt-1的突变体在几代内能够正常繁殖,但最终会因端粒侵蚀和染色体端对端融合而变得不育。端粒侵蚀和去帽不会导致trt-1突变体生殖系中细胞凋亡增加。相反,晚期trt-1突变体表现出染色体分离缺陷,这可能是不育的直接原因。trt-1与mrt-2在相同的端粒复制途径中发挥作用,mrt-2是Rad9/Rad1/Hus1(9-1-1)增殖细胞核抗原样滑动夹的一个组成部分。因此,9-1-1复合物可能是端粒酶在秀丽隐杆线虫染色体末端发挥作用所必需的。虽然端粒侵蚀限制了人类体细胞的复制寿命,但trt-1和端粒缩短都不会影响秀丽隐杆线虫的有丝分裂后衰老。这些发现说明了缺乏端粒酶催化亚基trt-1的秀丽隐杆线虫突变体中端粒功能障碍的影响。