Abstract
We studied the level of spontaneous telomere dysfunction in Rattus norvegicus (Berkenhout, 1769) (Rodentia, Muridae) embryonic fibroblasts (rEFs) and in cultured in vitro rat pluripotent stem cells (rPSCs), embryonic stem cells (rESCs) and induced pluripotent stem cells (riPSCs), on early passages and after prolonged cultivation. Among studied cell lines, rESCs showed the lowest level of telomere dysfunction, while the riPSCs demonstrated an elevated level on early passages of cultivation. In cultivation, the frequency of dysfunctional telomeres has increased in all studied cell lines; this is particularly true for dysfunctional telomeres occurring in G1 stage in riPSCs. The obtained data are mainly discussed in the connection with the specific structure of the telomere regions and their influence on the differential DNA damage response in them.
Highlights
Telomeres are specialized structures on animal chromosome ends; they preserve chromosomes from degradation and end-to-end fusions contributing to genome stability and play an important role in the maintenance of chromosome integrity
The normal human cells proved to be resistant to four spontaneous DDR+ telomeres arose in G1 cell phase (Kaul et al 2011)
A fluorescent signal located on one of the two sister chromatids demonstrates the chromatid type of dysfunction (Meta-TIF of chromatid type) that has arisen after DNA replication while signals located on both sister chromatids on the one chromosomal arm confirm the chromosome type dysfunction (Meta-TIF of chromosome type) arose in prereplication period (Cesare et al 2009, Kaul et al 2011) (Fig. 1)
Summary
Telomeres are specialized structures on animal chromosome ends; they preserve chromosomes from degradation and end-to-end fusions contributing to genome stability and play an important role in the maintenance of chromosome integrity. The lagging strand of telomeric DNA consists of repeat arrays of TTAGGG and are ended by G-rich overhang, which inserts into double strand telomere region forming t-loop. The chromosome ends are no longer recognized as DSBs (Double Strand Breaks). Telomere shortening or any DNA lesions, disruption of telomere capping or any telomere deprotection contribute to telomere dysfunction and further replicative senescence, apoptosis, frequent chromosomal rearrangements, degenerative diseases and cancer (Karlseder et al 2002, Kaul et al 2011, Cesare et al 2013). It has been shown earlier that one unrepaired DSB in a whole genome is able to direct cells towards the replicative senescence (di Leonardo et al 1994). The data about the level of telomere dysfunction in other mammalian species and in different tissue including pluripotent stem cells are restricted
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
