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MRT-2 checkpoint protein is required for germline immortality and telomere replication in C. elegans

Nature volume 403, pages 159–164 (2000)Cite this article

Abstract

The germ line is an immortal cell lineage that is passed indefinitely from one generation to the next. To identify the genes that are required for germline immortality, we isolated Caenorhabditis elegans mutants with mortal germ lines—worms that can reproduce for several healthy generations but eventually become sterile. One of these mortal germline (mrt ) mutants, mrt-2, exhibits progressive telomere shortening and accumulates end-to-end chromosome fusions in later generations, indicating that the MRT-2 protein is required for telomere replication. In addition, the germ line of mrt-2 is hypersensitive to X-rays and to transposon activity. Therefore, mrt-2 has defects in responding both to damaged DNA and to normal double-strand breaks present at telomeres. mrt-2 encodes a homologue of a checkpoint gene that is required to sense DNA damage in yeast. These results indicate that telomeres may be identified as a type of DNA damage and then repaired by the telomere-replication enzyme telomerase.

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Figure 1: The generation at sterility for 16 mortal germline mutants.
Figure 2: The Mortal Germline phenotype of mrt-2.
Figure 3: mrt-2 has defects in responding to DNA damage.
Figure 4: mrt-2 exhibits late-onset end-to-end chromosome fusions.
Figure 5: mrt-2 has a progressive telomere-shortening phenotype.
Figure 6: mrt-2 encodes a homologue of the S. pombe rad1+ and S. cerevisiae RAD17 checkpoint genes.

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Acknowledgements

We thank R. Hill, R. H. A. Plasterk and P. Kuwabara for advice and discussions; K. Van Auken for nob-1 (ct230); F. Müller and A. Coulson for plasmids; and A. Gartner, K. J. Patel, R. Harris, M. O'Reilly, D. Rhodes, V. P. C. C. Yu, A. Woollard, N. Hopper, M. Bickle, S. Sokol, and C. Milne for discussions and comments on this manuscript. Some strains were from the C. elegans Genetics Center (St. Paul, Minnesota), which is supported by the National Center for Research Resources. This work was supported by the Medical Research Council UK and the Howard Hughes Medical Institute. S.A. is a recipient of a Burroughs Wellcome Fund Hitchings-Elion Fellowship.

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    Shawn Ahmed & Jonathan Hodgkin

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Correspondence to Shawn Ahmed.

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Ahmed, S., Hodgkin, J. MRT-2 checkpoint protein is required for germline immortality and telomere replication in C. elegans. Nature 403, 159–164 (2000). https://doi.org/10.1038/35003120

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