tberardini
commented
7 years ago I'm not sure what you mean by " between GO:0000723 telomere maintenance and GO:0090656 t-circle formation (or better suggestions)." but I think we could add 'telomere maintenance via telomere trimming' as a sibling of those two terms and a direct child of 'telomere maintenance'.
The snippet of text you pasted, "telomere trimming, which is controlled by XRCC3 and Nbs1, homologous recombination proteins that generate single-stranded C-rich telomeric DNA and double-stranded telomeric circular DNA (T-circles), respectively." suggests that t-circle formation could be part of telomere trimming. Or am I taking this phrase out of context and those two processes (telomere trimming and t-circle formation) are distinctly different?
NancyCampbell
PMID 27918544 Nat Struct Mol Biol. 2017 Jan A balance between elongation and trimming regulates telomere stability in stem cells. Rivera T1, Haggblom C1, Cosconati S2, Karlseder J1.
This very recent paper describes active trimming of telomeres which contributes to telomere maintenance i.e. actively making telomeres shorter,
Author states: "Telomere length maintenance ensures self-renewal of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs); however, the mechanisms governing telomere length homeostasis in these cell types are unclear. Here, we report that telomere length is determined by the balance between telomere elongation, which is mediated by telomerase, and telomere trimming, which is controlled by XRCC3 and Nbs1, homologous recombination proteins that generate single-stranded C-rich telomeric DNA and double-stranded telomeric circular DNA (T-circles), respectively."
Author states: "We found that reprogramming of differentiated cells induces T-circle and single-stranded C-rich telomeric DNA accumulation, indicating the activation of telomere trimming pathways that compensate telomerase-dependent telomere elongation in hiPSCs".
Historically, T-circle formation has been mostly associated with ALT cells which are not normal cells (ALT mechanism occurs in 15% of cancer cells).
However, more recently, evidence emerged which indicates that T-circle formation is part of a normal process which actively shortens telomeres in normal cells. Please note that there are many papers related to T-circle formation but in context of ALT cells which are not normal so are not relevant here. Evidence in normal cells includes:
the publication outlined above PMID 27918544: Nat Struct Mol Biol. 2017 Jan A balance between elongation and trimming regulates telomere stability in stem cells.
PMID: 21903669 Hum Mol Genet. 2011 Normal mammalian cells negatively regulate telomere length by telomere trimming.
I have not looked outside mammals but there might be more evidence? (or not)? in other organisms (not sure if there is a model for ALT and non-ALT)?
In contrast, telomere lengthening - via telomerase - has long been the active process. Hence, I would like advice please.
Is it approriate to create a
Telomere maintenance via telomere trimming placed between GO:0000723 telomere maintenance and GO:0090656 t-circle formation (or better suggestions).
Please advise. Thanks.