rg: NTR: telomeric 3' overhang cleavage

[gocentral]

In GO there is a term "telomeric 3' overhang formation" GO:0031860. I would like the term "telomeric 3' overhang cleavage/removal" based on PMID:14690602 which shows that the ERCC1/XPF complex cleaves the 3' G-strand overhang of telomeres providing a substrate for non-homologous end joining (NHEJ).

I guess it would be a child of "telomere maintenance" GO:0000723.

Thanks, Rachael.

Reported by: rachhuntley

Original Ticket: "geneontology/ontology-requests/4583":https://sourceforge.net/p/geneontology/ontology-requests/4583

[gocentral]

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Synonym of "telomeric 3' overhang cleavage" is "G-strand processing" PMID:16762604

Original comment by: rachhuntley

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Synonym of "telomeric 3' overhang cleavage" is "G-strand processing" PMID:16762604

Original comment by: rachhuntley

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Is removal of the 3' overhang a normal process? The papers give the impression that it's seen in mutants (tho I did just skim them quickly).

m

Original comment by: mah11

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So, my understanding (gleaned from various papers including PMIDs:16142233 and 14690602) is this; The T loop protects the single-stranded 3' chromosome end (G-strand overhang) from degradation and repair activities. The telomere-binding protein TRF2 is a crucial player in telomere protection and is involved in facilitating the formation of T loops. Telomere shortening or loss of function of telomere-binding proteins (including TRF2) results in loss of telomere protection, end-to-end chromosome fusions and cell-cycle arrest or apoptosis. If TRF2 is lost then the 3' overhang of the telomere is cleaved in a process which somehow requires the XPF-ERCC1 nuclease. Whether it is a natural occurence for TRF2 to be lost from the ends of telomeres, I don't know, presumably it could be - but most papers use RNAi or a dominant negative allele to inhibit it. Whatever the cause of loss of TRF2, it appears then that the natural event is for the affected telomeres to be shortened by cleavage of the 3' overhang. The papers use mutants of XPF to show there is no loss of the 3' overhang, whereas those with wild type XPF do have loss of the overhang (in cells where TRF2 has been inhibited).

Do you know of anyone who could give their opinion?

Rachael.

Original comment by: rachhuntley

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Unfortunately I don't have any contacts in the telomere research community. I do know that Titia de Lange is one of the big names, as is Elizabeth Blackburn.

I don't know whether TRF2 is normally lost from telomeres, but I haven't (so far) found any papers that say it is. Certainly telomere fusion (as can occur in the absence of TRF2 and presence of XPF-ERCC1) isn't normal, and that makes me suspect that TRF2 loss is abnormal.

m

Original comment by: mah11

[gocentral]

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I wrote to Titia de Lange who has confirmed that telomeric 3' overhang removal is a pathological event, i.e. not normal - so we can forget this one.

Rachael.

Original comment by: rachhuntley

[gocentral]

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OK; thanks for investigating!

m

Original comment by: mah11

[gocentral]

• status: open --> closed-rejected

Original comment by: mah11