scholarly journals Ccq1-Tpz1TPP1 interaction facilitates telomerase and SHREC association with telomeres in fission yeast

2015 ◽  
Vol 26 (21) ◽  
pp. 3857-3866 ◽  
Author(s):  
Bettina A. Moser ◽  
Olga N. Raguimova ◽  
Toru M. Nakamura
Keyword(s):  
Dna Damage ◽  
Fission Yeast ◽  
Telomere Maintenance ◽  
Dna Damage Checkpoint ◽  
Checkpoint Activation ◽  
Telomere Shortening ◽  
Progressive Loss ◽  
Evolutionarily Conserved ◽  
Repressor Complex

Evolutionarily conserved shelterin complex is essential for telomere maintenance in the fission yeast Schizosaccharomyces pombe. Elimination of the fission yeast shelterin subunit Ccq1 causes progressive loss of telomeres due to the inability to recruit telomerase, activates the DNA damage checkpoint, and loses heterochromatin at telomere/subtelomere regions due to reduced recruitment of the heterochromatin regulator complex Snf2/histone deacetylase–containing repressor complex (SHREC). The shelterin subunit Tpz1TPP1 directly interacts with Ccq1 through conserved C-terminal residues in Tpz1TPP1, and tpz1 mutants that fail to interact with Ccq1 show telomere shortening, checkpoint activation, and loss of heterochromatin. While we have previously concluded that Ccq1-Tpz1TPP1 interaction contributes to Ccq1 accumulation and telomerase recruitment based on analysis of tpz1 mutants that fail to interact with Ccq1, another study reported that loss of Ccq1-Tpz1TPP1 interaction does not affect accumulation of Ccq1 or telomerase. Furthermore, it remained unclear whether loss of Ccq1-Tpz1TPP1 interaction affects SHREC accumulation at telomeres. To resolve these issues, we identified and characterized a series of ccq1 mutations that disrupt Ccq1-Tpz1TPP1 interaction. Characterization of these ccq1 mutants established that Ccq1-Tpz1TPP1 interaction contributes to optimal binding of the Ccq1-SHREC complex, and is critical for Rad3ATR/Tel1ATM-dependent Ccq1 Thr93 phosphorylation and telomerase recruitment.

scholarly journals Slx4 Regulates DNA Damage Checkpoint-dependent Phosphorylation of the BRCT Domain Protein Rtt107/Esc4

2006 ◽  
Vol 17 (1) ◽  
pp. 539-548 ◽  
Author(s):  
Tania M. Roberts ◽  
Michael S. Kobor ◽  
Suzanne A. Bastin-Shanower ◽  
Miki Ii ◽  
Sonja A. Horte ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Dna Damage Checkpoint ◽  
Checkpoint Activation ◽  
Alkylation Damage ◽  
Binding Partner ◽  
Replication Restart ◽  
Damage Response ◽  
Domain Protein

RTT107 (ESC4, YHR154W) encodes a BRCA1 C-terminal-domain protein that is important for recovery from DNA damage during S phase. Rtt107 is a substrate of the checkpoint protein kinase Mec1, although the mechanism by which Rtt107 is targeted by Mec1 after checkpoint activation is currently unclear. Slx4, a component of the Slx1-Slx4 structure-specific nuclease, formed a complex with Rtt107. Deletion of SLX4 conferred many of the same DNA-repair defects observed in rtt107Δ, including DNA damage sensitivity, prolonged DNA damage checkpoint activation, and increased spontaneous DNA damage. These phenotypes were not shared by the Slx4 binding partner Slx1, suggesting that the functions of the Slx4 and Slx1 proteins in the DNA damage response were not identical. Of particular interest, Slx4, but not Slx1, was required for phosphorylation of Rtt107 by Mec1 in vivo, indicating that Slx4 was a mediator of DNA damage-dependent phosphorylation of the checkpoint effector Rtt107. We propose that Slx4 has roles in the DNA damage response that are distinct from the function of Slx1-Slx4 in maintaining rDNA structure and that Slx4-dependent phosphorylation of Rtt107 by Mec1 is critical for replication restart after alkylation damage.

scholarly journals Monitoring S. pombe genome stress by visualizing end-binding protein Ku

2020 ◽  
Author(s):  
Chance Jones ◽  
Susan L Forsburg
Keyword(s):  
Dna Damage ◽  
Fission Yeast ◽  
Protein Complex ◽  
Genome Stability ◽  
Binding Protein ◽  
Dna Lesions ◽  
Live Cells ◽  
Dna Damage Checkpoint ◽  
Unique Pattern ◽  
Ku Protein

AbstractStudies of genome stability have exploited visualization of fluorescently tagged proteins in live cells to characterize DNA damage, checkpoint, and repair responses. In this report, we describe a new tool for fission yeast, a tagged version of the end-binding protein Pku70 which is part of the KU protein complex. We compare Pku70 localization to other markers upon treatment to various genotoxins, and identify a unique pattern of distribution. Pku70 provides a new tool to define and characterize DNA lesions and the repair response.

scholarly journals The Yeast PCNA Unloader Elg1 RFC-Like Complex Plays a Role in Eliciting the DNA Damage Checkpoint

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Soumitra Sau ◽  
Batia Liefshitz ◽  
Martin Kupiec
Keyword(s):  
Dna Damage ◽  
Dna Replication ◽  
Cellular Response ◽  
Genome Stability ◽  
Adaptor Proteins ◽  
Nuclear Antigen ◽  
Dna Damage Checkpoint ◽  
Activation Process ◽  
Checkpoint Activation ◽  
Dna Replication And Repair

ABSTRACT The PCNA (proliferating cell nuclear antigen) ring plays central roles during DNA replication and repair. The yeast Elg1 RFC-like complex (RLC) is the principal unloader of chromatin-bound PCNA and thus plays a central role in maintaining genome stability. Here we identify a role for Elg1 in the unloading of PCNA during DNA damage. Using DNA damage checkpoint (DC)-inducible and replication checkpoint (RC)-inducible strains, we show that Elg1 is essential for eliciting the signal in the DC branch. In the absence of Elg1 activity, the Rad9 (53BP1) and Dpb11 (TopBP1) adaptor proteins are recruited but fail to be phosphorylated by Mec1 (ATR), resulting in a lack of checkpoint activation. The chromatin immunoprecipitation of PCNA at the Lac operator sites reveals that accumulated local PCNA influences the checkpoint activation process in elg1 mutants. Our data suggest that Elg1 participates in a mechanism that may coordinate PCNA unloading during DNA repair with DNA damage checkpoint induction. IMPORTANCE The Elg1protein forms an RFC-like complex in charge of unloading PCNA from chromatin during DNA replication and repair. Mutations in the ELG1 gene caused genomic instability in all organisms tested and cancer in mammals. Here we show that Elg1 plays a role in the induction of the DNA damage checkpoint, a cellular response to DNA damage. We show that this defect is due to a defect in the signal amplification process during induction. Thus, cells coordinate the cell's response and the PCNA unloading through the activity of Elg1.

53BP1: function and mechanisms of focal recruitment

2009 ◽  
Vol 37 (4) ◽  
pp. 897-904 ◽  
Author(s):  
Jennifer E. FitzGerald ◽  
Muriel Grenon ◽  
Noel F. Lowndes
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Dna Damage Response ◽  
Dna Damage Checkpoint ◽  
Checkpoint Activation ◽  
Damage Response ◽  
Nuclear Structures ◽  
Genotoxic Insult ◽  
Covalent Histone Modifications

53BP1 (p53-binding protein 1) is classified as a mediator/adaptor of the DNA-damage response, and is recruited to nuclear structures termed foci following genotoxic insult. In the present paper, we review the functions of 53BP1 in DNA-damage checkpoint activation and DNA repair, and the mechanisms of its recruitment and activation following DNA damage. We focus in particular on the role of covalent histone modifications in this process.

DNA Damage Checkpoint Control of Mitosis in Fission Yeast

2000 ◽  
Vol 65 (0) ◽  
pp. 353-360 ◽  
Author(s):  
N. RHIND ◽  
B.A. BABER-FURNARI ◽  
A. LOPEZ-GIRONA ◽  
M.N. BODDY ◽  
J.-M. BRONDELLO ◽  
...  
Keyword(s):  
Dna Damage ◽  
Fission Yeast ◽  
Dna Damage Checkpoint ◽  
Checkpoint Control

scholarly journals Repo-Man Controls a Protein Phosphatase 1-Dependent Threshold for DNA Damage Checkpoint Activation

2010 ◽  
Vol 20 (5) ◽  
pp. 387-396 ◽  
Author(s):  
Aimin Peng ◽  
Andrea L. Lewellyn ◽  
William P. Schiemann ◽  
James L. Maller
Keyword(s):  
Dna Damage ◽  
Protein Phosphatase ◽  
Protein Phosphatase 1 ◽  
Dna Damage Checkpoint ◽  
Checkpoint Activation
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