scholarly journals Cell cycle–dependent spatial segregation of telomerase from sites of DNA damage

2017 ◽  
Vol 216 (8) ◽  
pp. 2355-2371 ◽  
Author(s):  
Faissal Ouenzar ◽  
Maxime Lalonde ◽  
Hadrien Laprade ◽  
Geneviève Morin ◽  
Franck Gallardo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Single Molecule ◽  
De Novo ◽  
Dependent Manner ◽  
Dna Double Strand Breaks ◽  
Yeast Telomerase ◽  
A Cell ◽  
Spatial Exclusion ◽  
Cycle Dependent

Telomerase can generate a novel telomere at DNA double-strand breaks (DSBs), an event called de novo telomere addition. How this activity is suppressed remains unclear. Combining single-molecule imaging and deep sequencing, we show that the budding yeast telomerase RNA (TLC1 RNA) is spatially segregated to the nucleolus and excluded from sites of DNA repair in a cell cycle–dependent manner. Although TLC1 RNA accumulates in the nucleoplasm in G1/S, Pif1 activity promotes TLC1 RNA localization in the nucleolus in G2/M. In the presence of DSBs, TLC1 RNA remains nucleolar in most G2/M cells but accumulates in the nucleoplasm and colocalizes with DSBs in rad52Δ cells, leading to de novo telomere additions. Nucleoplasmic accumulation of TLC1 RNA depends on Cdc13 localization at DSBs and on the SUMO ligase Siz1, which is required for de novo telomere addition in rad52Δ cells. This study reveals novel roles for Pif1, Rad52, and Siz1-dependent sumoylation in the spatial exclusion of telomerase from sites of DNA repair.

scholarly journals Dynamic Alterations of Histone H3 Phospho-acetylation Correlate With Radio Sensitivity of Mitotic Cells During DNA Damage

2020 ◽  
Author(s):  
Asmita Sharda ◽  
Tripti Verma ◽  
Nikhil Gadewal ◽  
Sanjay Gupta
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Repair ◽  
Cell Cycle Progression ◽  
Protein Translation ◽  
Chemotherapeutic Agents ◽  
Open Chromatin ◽  
Dependent Manner ◽  
A Cell ◽  
Cycle Dependent

Abstract Background - Histone Post Translational Modifications (PTMs) change in a cell cycle dependent manner and also orchestrate the DNA repair process for radiation induced DNA damage. Mitosis is the most radiosensitive phase of the cell cycle but the epigenetic events that regulate its radiosensitivity remain elusive.Results - This study explored the dynamics between histone marks H3S10/S28ph, H3K9ac and γH2AX during mitotic DNA damage response. The presence of a mononucleosome level association between γH2AX and H3S10ph was observed only during mitosis. This association was abrogated upon cell cycle progression and chromatin de-condensation, concomitant with chromatin recruitment of DNA repair proteins Ku70 and Rad51. Moreover, the levels of H3S10/28ph remained unchanged upon DNA damage during mitosis, but decreased in a cell cycle dependent manner upon mitotic exit. However, the population that arose after mitotic progression of damaged cells comprised of binucleated tetraploid cells. This population was epigenetically distinct from interphase cells, characterized by reduced H3S10/S28ph, increased H3K9ac and more open chromatin configuration. These epigenetic features correlated with decreased survival potential of this population. The low levels of H3S10/28ph were attributed to decreased protein translation and chromatin recruitment of histone kinase Mitogen and Stress-activated Kinase 1 (MSK1) along with persistent levels of Protein phosphatase1 catalytic subunit α (PP1α). Conclusions – This study suggests that a unique epigenetic landscape attained during and after mitotic DNA damage collectively contributed to mitotic radiosensitivity. The findings of this study have potential clinical significance in terms of tackling resistance against anti-mitotic chemotherapeutic agents.

scholarly journals De novo telomere addition at chromosome breaks: Dangerous Liaisons

2017 ◽  
Vol 216 (8) ◽  
pp. 2243-2245 ◽  
Author(s):  
Dmitri Churikov ◽  
Vincent Géli
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Dna Sequences ◽  
De Novo ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Telomeric Repeats ◽  
Strand Breaks ◽  
Chromosome Breaks ◽  
Cycle Dependent

Telomerase counteracts the loss of terminal DNA sequences from chromosome ends; however, it may erroneously add telomeric repeats to DNA double-strand breaks. In this issue, Ouenzar et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201610071) uncover cell cycle–dependent sequestration of the telomerase RNA in nucleoli, a process that excludes telomerase from DNA repair sites.

scholarly journals Truncated APC regulates the transcriptional activity of β-catenin in a cell cycle dependent manner

2006 ◽  
Vol 16 (2) ◽  
pp. 199-209 ◽  
Author(s):  
Jean Schneikert ◽  
Annette Grohmann ◽  
Jürgen Behrens
Keyword(s):  
Cell Cycle ◽  
Transcriptional Activity ◽  
Dependent Manner ◽  
A Cell ◽  
Cycle Dependent

scholarly journals Ser68 phosphoregulation is essential for CENP-A deposition, centromere function and viability in mice

2021 ◽  
Author(s):  
Yuting Liu ◽  
Kehui Wang ◽  
Li Huang ◽  
Jicheng Zhao ◽  
Xinpeng Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Histone H3 ◽  
Dependent Manner ◽  
Centromere Function ◽  
Histone H3 Variant ◽  
A Cell ◽  
Cycle Dependent ◽  
Spatiotemporal Control

Centromere identity is defined by nucleosomes containing CENP-A, a histone H3 variant. The deposition of CENP-A at centromeres is tightly regulated in a cell-cycle-dependent manner. We previously reported that the spatiotemporal control of centromeric CENP-A incorporation is mediated by the phosphorylation of CENP-A Ser68. However, a recent report argued that Ser68 phosphoregulation is dispensable for accurate CENP-A loading. Here, we report that the substitution of Ser68 of endogenous CENP-A with either Gln68 or Glu68 severely impairs CENP-A deposition and cell viability. We also find that mice harboring the corresponding mutations are lethal. Together, these results indicate that the dynamic phosphorylation of Ser68 ensures cell-cycle-dependent CENP-A deposition and cell viability.

scholarly journals Gcn5-mediated acetylation at MBF-regulated promoters induces the G1/S transcriptional wave

2019 ◽  
Vol 47 (16) ◽  
pp. 8439-8451 ◽  
Author(s):  
Alberto González-Medina ◽  
Elena Hidalgo ◽  
José Ayté
Keyword(s):  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Histone H3 ◽  
Dependent Manner ◽  
Saga Complex ◽  
Lysine Residues ◽  
Physical Barriers ◽  
A Cell ◽  
Cycle Dependent ◽  
Regulated Promoters

Abstract In fission yeast, MBF-dependent transcription is inactivated at the end of S phase through a negative feedback loop that involves the co-repressors, Yox1 and Nrm1. Although this repression system is well known, the molecular mechanisms involved in MBF activation remain largely unknown. Compacted chromatin constitutes a barrier to activators accessing promoters. Here, we show that chromatin regulation plays a key role in activating MBF-dependent transcription. Gcn5, a part of the SAGA complex, binds to MBF-regulated promoters through the MBF co-activator Rep2 in a cell cycle-dependent manner and in a reverse correlation to the binding of the MBF co-repressors, Nrm1 or Yox1. We propose that the co-repressors function as physical barriers to SAGA recruitment onto MBF promoters. We also show that Gcn5 acetylates specific lysine residues on histone H3 in a cell cycle-regulated manner. Furthermore, either in a gcn5 mutant or in a strain in which histone H3 is kept in an unacetylated form, MBF-dependent transcription is downregulated. In summary, Gcn5 is required for the full activation and correct timing of MBF-regulated gene transcription.

scholarly journals Correction: Optineurin Regulates the Interferon Response in a Cell Cycle-Dependent Manner

2015 ◽  
Vol 11 (6) ◽  
pp. e1004971 ◽  
Author(s):  
Pierre Génin ◽  
Frédérique Cuvelier ◽  
Sandrine Lambin ◽  
Josina Côrte-Real Filipe ◽  
Elodie Autrusseau ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Interferon Response ◽  
Dependent Manner ◽  
A Cell ◽  
Cycle Dependent

Importin α/β-mediated nuclear protein import is regulated in a cell cycle-dependent manner

2004 ◽  
Vol 297 (1) ◽  
pp. 285-293 ◽  
Author(s):  
Noriko Yasuhara ◽  
Eri Takeda ◽  
Hitomi Inoue ◽  
Ippei Kotera ◽  
Yoshihiro Yoneda
Keyword(s):  
Cell Cycle ◽  
Protein Import ◽  
Nuclear Protein ◽  
Dependent Manner ◽  
Importin Α ◽  
A Cell ◽  
Nuclear Protein Import ◽  
Cycle Dependent

scholarly journals A Cell Cycle-Dependent Regulatory Circuit Composed of 53BP1-RIF1 and BRCA1-CtIP Controls DNA Repair Pathway Choice

2013 ◽  
Vol 49 (5) ◽  
pp. 872-883 ◽  
Author(s):  
Cristina Escribano-Díaz ◽  
Alexandre Orthwein ◽  
Amélie Fradet-Turcotte ◽  
Mengtan Xing ◽  
Jordan T.F. Young ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Repair Pathway ◽  
Regulatory Circuit ◽  
A Cell ◽  
Pathway Choice ◽  
Cycle Dependent
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