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.
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http://dx.doi.org/10.1371/journal.pgen.0020018 | DOI Listing |
Cold Spring Harb Perspect Biol
November 2024
Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom
Telomere function is critical for genomic stability; in the context of a functional TP53 response, telomere erosion leads to a G/S cell-cycle arrest and the induction of replicative senescence, a process that is considered to underpin the ageing process in long-lived species. Abrogation of the TP53 pathway allows for continued cell division, telomere erosion, and the complete loss of telomere function; the ensuing genomic instability facilitates clonal evolution and malignant progression. Telomeres display extensive length heterogeneity in the population that is established at birth, and this affects the individual risk of a broad range of diseases, including cardiovascular disease and cancer.
View Article and Find Full Text PDFInt J Rheum Dis
November 2024
Theme Women's Health and Allied Health Professionals, Medical Unit Allied Health Professionals, Karolinska University Hospital, and Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden.
DNA Repair (Amst)
October 2024
Department of Biochemistry & Structural Biology, University of Texas Health San Antonio, San Antonio, TX 78229, USA. Electronic address:
Break-induced replication (BIR) is a homologous recombination (HR) pathway that repairs one-ended DNA double-strand breaks (DSBs), which can result from replication fork collapse, telomere erosion, and other events. Eukaryotic BIR has been mainly investigated in yeast, where it is initiated by invasion of the broken DNA end into a homologous sequence, followed by extensive replication synthesis proceeding to the chromosome end. Multiple recent studies have described BIR in mammalian cells, the properties of which show many similarities to yeast BIR.
View Article and Find Full Text PDFJ Appl Genet
December 2024
Department of Salmonid Research, Inland Fisheries Institute in Olsztyn, Rutki, 83-330, Żukowo, Poland.
Expression of the telomerase reverse-transcriptase (TERT) gene and activity of telomerase have been reported in the somatic tissues and gonads in fish irrespective of their age and size. Nevertheless, little is known about TERT expression in the fish eggs. In the current study, the presence of the TERT transcripts was confirmed in the rainbow trout ovulated eggs before and after activation with nonirradiated and UV-irradiated (gynogenesis) sperm.
View Article and Find Full Text PDFLife (Basel)
March 2024
Australian Centre for Antimicrobial Resistance Ecology, School of Animal & Veterinary Sciences, University of Adelaide, Roseworthy Campus, Roseworthy, SA 5371, Australia.
Cells are very important to researchers due to their use in various biological studies in and settings. This importance stems from the short lifespan of most cells under laboratory conditions, which can pose significant challenges, such as the difficulties associated with extraction from the source tissue, ethical concerns about separating cells from human or animal models, limited cell passage ability, and variation in results due to differences in the source of the obtained cells, among other issues. In general, cells in laboratory conditions can divide into a limited number, known as the Hayflick limit, due to telomere erosion at the end of each cellular cycle.
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