ALT Telomeres Borrow from Meiosis to Get Moving

Telomere clustering is required for the homologous recombination events that maintain chromosome ends in cells relying on alternative lengthening of telomeres (ALT). New data demonstrate that damage signaling at telomeres, a likely step in activating maintenance mechanisms, induces directional movement and synapsis driven by the machinery responsible for recombination in meiosis

The heterochromatic chromosome caps in great apes impact telomere metabolism.

In contrast with the limited sequence divergence accumulated after separation of higher primate lineages, marked cytogenetic variation has been associated with the genome evolution in these species. Studying the impact of such structural variations on defined molecular processes can provide valuable insights on how genome structural organization contributes to organismal evolution. Here, we show that telomeres on chromosome arms carrying subtelomeric heterochromatic caps in the chimpanzee, which are completely absent in humans, replicate later than telomeres on chromosome arms without caps. In gorilla, on the other hand, a proportion of the subtelomeric heterochromatic caps present in most chromosome arms are associated with large blocks of telomere-like sequences that follow a replication program different from that of bona fide telomeres. Strikingly, telomere-containing RNA accumulates extrachromosomally in gorilla mitotic cells, suggesting that at least some aspects of telomere-containing RNA biogenesis have diverged in gorilla, perhaps in concert with the evolution of heterochromatic caps in this species

The APE2 nuclease is essential for DNA double strand break repair by microhomology-mediated end-joining.

Amplicon sequencing: CRISPR-Cas9 screens and DNA repair sequencin

Mechanisms of telomere replication in mammals

Les télomères sont des structures nucléoprotéiques qui protègent les extrémités des chromosomes et constituent l horloge mitotique de la cellule. Comprendre leur réplication est donc essentielle pour mieux appréhender les processus de vieillissement et de cancer. Au sein du laboratoire d Arturo Londoño, nous avons donc essayé de caractériser plusieurs aspects de la réplication des télomères chez les mammifères.Nous avons d abord pu montrer que chaque télomère se réplique à un moment préférentiel de la phase S, qui est conservé, régule , et influencé notamment par certains éléments hétérochromatinisants ainsi qu une localisation nucléaire périphérique.D autre part, nous avons montré que l hélicase WRN était essentielle à la progression de la fourche de réplication au sein des répétitions télomériques. En son absence, il y a découplage entre la réplication en continu et discontinu. POT1 protègerait le simple brin accumulé sur le brin répliqué en discontinu, ce qui permettrait ce découplage en empêchant l activation d un point de contrôlePARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Telomeric RNA expression: length matters.

A commentary on TERRA expression levels do not correlate with telomere length and radiation sensitivity in human cancer cell line

Polycomb repressive complex 2 and H3K27me3 cooperate with H3K9 methylation to maintain heterochromatin protein 1α at chromatin.

Methylation of histone H3 on lysine 9 or 27 is crucial for heterochromatin formation. Previously considered hallmarks of, respectively, constitutive and facultative heterochromatin, recent evidence has accumulated in favor of coexistence of these two marks and their cooperation in gene silencing maintenance. H3K9me2/3 ensures anchorage at chromatin of heterochromatin protein 1α (HP1α), a main component of heterochromatin. HP1α chromoshadow domain, involved in dimerization and interaction with partners, has additional but still unclear roles in HP1α recruitment to chromatin. Because of previously suggested links between polycomb repressive complex 2 (PRC2), which catalyzes H3K27 methylation, and HP1α, we tested whether PRC2 may regulate HP1α abundance at chromatin. We found that the EZH2 and SUZ12 subunits of PRC2 are required for HP1α stability, as knockdown of either protein led to HP1α degradation. Similar results were obtained upon overexpression of H3K27me2/3 demethylases. We further showed that binding of HP1α/β/γ to H3K9me3 peptides is greatly increased in the presence of H3K27me3, and this is dependent on PRC2. These data fit with recent proteomic studies identifying PRC2 as an indirect H3K9me3 binder in mouse tissues and suggest the existence of a cooperative mechanism of HP1α anchorage at chromatin involving H3 methylation on both K9 and K27 residues

Telomeric chromatin regulates human telomere transcription

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