Limits...
Telomere stability and development of ctc1 mutants are rescued by inhibition of EJ recombination pathways in a telomerase-dependent manner.

Amiard S, Olivier M, Allain E, Choi K, Smith-Unna R, Henderson IR, White CI, Gallego ME - Nucleic Acids Res. (2014)

Bottom Line: In this work, we set out to specifically test this hypothesis in the plant, Arabidopsis.It is thus the chromosomal fusions, per se, which are the underlying cause of the severe developmental defects.This rescue is mediated by telomerase-dependent telomere extension, revealing a competition between telomerase and end-joining recombination proteins for access to deprotected telomeres.

View Article: PubMed Central - PubMed

Affiliation: Génétique, Reproduction et Développement, UMR CNRS 6293, Clermont Université, INSERM U1103, Aubière, France megalleg@univ-bpclermont.fr.

Show MeSH

Related in: MedlinePlus

Competition between telomerase and the EJ recombination pathways at unprotected telomeres. The CST complex controls access of telomerase and EJ recombination to the chromosome ends in WT plants (a). In the absence of a functional CST complex (b), KU restricts access of telomerase to the free end and telomere shortening and fusions result in defects in growth and development. In the absence of both CST and KU (c), competition between alternative EJ pathways and telomerase results in both telomere lengthening and the presence of telomere fusions, accompanied by severe growth defects. Removal of these alternative EJ pathways in cst ku80 xrcc1 xpf mutants (d) opens access of telomerase to chromosome ends, extending telomeres and avoiding chromosome fusion and growth defects. Telomere loss and very high levels of chromosome fusions are seen in plants lacking CST, the EJ pathways and telomerase (e), and these plants show severe growth defects. See the text for details.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4231758&req=5

Figure 7: Competition between telomerase and the EJ recombination pathways at unprotected telomeres. The CST complex controls access of telomerase and EJ recombination to the chromosome ends in WT plants (a). In the absence of a functional CST complex (b), KU restricts access of telomerase to the free end and telomere shortening and fusions result in defects in growth and development. In the absence of both CST and KU (c), competition between alternative EJ pathways and telomerase results in both telomere lengthening and the presence of telomere fusions, accompanied by severe growth defects. Removal of these alternative EJ pathways in cst ku80 xrcc1 xpf mutants (d) opens access of telomerase to chromosome ends, extending telomeres and avoiding chromosome fusion and growth defects. Telomere loss and very high levels of chromosome fusions are seen in plants lacking CST, the EJ pathways and telomerase (e), and these plants show severe growth defects. See the text for details.

Mentions: The principal conclusions of this work concerning the roles of CST, telomerase and EJ recombination pathways at telomeres are summarized graphically in Figure 7. Absence of EJ pathways in ctc1 mutants not only ‘rescues’ the ability of these plants to develop normally but also results in telomere elongation. That this is due to elongation by telomerase is seen in the very severe telomere shortening and developmental defects when telomerase is absent in this genetic background: ctc1 ku80 xrcc1 xpf mutants appear normal, while ctc1 ku80 xrcc1 xpf tert mutants are very severely affected. This implies that EJ pathway proteins and telomerase compete for access of deprotected telomeres in the absence of CST. Such a competition with telomerase has already been described for the KU complex, with longer telomeres in ku70 mutants (39), ku80 mutants showing telomerase-dependent telomere elongation (38,39). Notwithstanding severe telomere destabilization, the absence of KU80 also gives increases in telomere length in stn1 (32) and ctc1 mutants (Supplementary Figure S2). We show here that XRCC1 and XPF restrict telomerase activity at telomeres in ctc1 ku80 mutants and hypothesize that this is due to an analogous effect of competition with telomerase for access to deprotected telomeres. Deprotected ctc1 ku80 xrcc1 xpf telomeres are thus elongated by telomerase and no longer fuse in the absence of both classical and alternative EJ pathways, resulting in the rescue of growth and developmental phenotypes (Figure 7d). Taking away the catalytic subunit of the telomerase in this context causes rapid telomeric loss, severe genomic instability, growth defects and sterility (Figure 7e).


Telomere stability and development of ctc1 mutants are rescued by inhibition of EJ recombination pathways in a telomerase-dependent manner.

Amiard S, Olivier M, Allain E, Choi K, Smith-Unna R, Henderson IR, White CI, Gallego ME - Nucleic Acids Res. (2014)

Competition between telomerase and the EJ recombination pathways at unprotected telomeres. The CST complex controls access of telomerase and EJ recombination to the chromosome ends in WT plants (a). In the absence of a functional CST complex (b), KU restricts access of telomerase to the free end and telomere shortening and fusions result in defects in growth and development. In the absence of both CST and KU (c), competition between alternative EJ pathways and telomerase results in both telomere lengthening and the presence of telomere fusions, accompanied by severe growth defects. Removal of these alternative EJ pathways in cst ku80 xrcc1 xpf mutants (d) opens access of telomerase to chromosome ends, extending telomeres and avoiding chromosome fusion and growth defects. Telomere loss and very high levels of chromosome fusions are seen in plants lacking CST, the EJ pathways and telomerase (e), and these plants show severe growth defects. See the text for details.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231758&req=5

Figure 7: Competition between telomerase and the EJ recombination pathways at unprotected telomeres. The CST complex controls access of telomerase and EJ recombination to the chromosome ends in WT plants (a). In the absence of a functional CST complex (b), KU restricts access of telomerase to the free end and telomere shortening and fusions result in defects in growth and development. In the absence of both CST and KU (c), competition between alternative EJ pathways and telomerase results in both telomere lengthening and the presence of telomere fusions, accompanied by severe growth defects. Removal of these alternative EJ pathways in cst ku80 xrcc1 xpf mutants (d) opens access of telomerase to chromosome ends, extending telomeres and avoiding chromosome fusion and growth defects. Telomere loss and very high levels of chromosome fusions are seen in plants lacking CST, the EJ pathways and telomerase (e), and these plants show severe growth defects. See the text for details.
Mentions: The principal conclusions of this work concerning the roles of CST, telomerase and EJ recombination pathways at telomeres are summarized graphically in Figure 7. Absence of EJ pathways in ctc1 mutants not only ‘rescues’ the ability of these plants to develop normally but also results in telomere elongation. That this is due to elongation by telomerase is seen in the very severe telomere shortening and developmental defects when telomerase is absent in this genetic background: ctc1 ku80 xrcc1 xpf mutants appear normal, while ctc1 ku80 xrcc1 xpf tert mutants are very severely affected. This implies that EJ pathway proteins and telomerase compete for access of deprotected telomeres in the absence of CST. Such a competition with telomerase has already been described for the KU complex, with longer telomeres in ku70 mutants (39), ku80 mutants showing telomerase-dependent telomere elongation (38,39). Notwithstanding severe telomere destabilization, the absence of KU80 also gives increases in telomere length in stn1 (32) and ctc1 mutants (Supplementary Figure S2). We show here that XRCC1 and XPF restrict telomerase activity at telomeres in ctc1 ku80 mutants and hypothesize that this is due to an analogous effect of competition with telomerase for access to deprotected telomeres. Deprotected ctc1 ku80 xrcc1 xpf telomeres are thus elongated by telomerase and no longer fuse in the absence of both classical and alternative EJ pathways, resulting in the rescue of growth and developmental phenotypes (Figure 7d). Taking away the catalytic subunit of the telomerase in this context causes rapid telomeric loss, severe genomic instability, growth defects and sterility (Figure 7e).

Bottom Line: In this work, we set out to specifically test this hypothesis in the plant, Arabidopsis.It is thus the chromosomal fusions, per se, which are the underlying cause of the severe developmental defects.This rescue is mediated by telomerase-dependent telomere extension, revealing a competition between telomerase and end-joining recombination proteins for access to deprotected telomeres.

View Article: PubMed Central - PubMed

Affiliation: Génétique, Reproduction et Développement, UMR CNRS 6293, Clermont Université, INSERM U1103, Aubière, France megalleg@univ-bpclermont.fr.

Show MeSH
Related in: MedlinePlus