scholarly journals Checkpoint Control of DNA Repair in Yeast

2021 ◽  
Author(s):  
Michael Fasullo
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Genetic Instability ◽  
Damage Tolerance ◽  
Model Organism ◽  
Checkpoint Control ◽  
Dna Damage Tolerance ◽  
Checkpoint Response ◽  
Phosphorylated Proteins ◽  
Bulky Dna Adducts

Budding yeast has been a model organism for understanding how DNA damage is repaired and how cells minimize genetic instability caused by arresting or delaying the cell cycle at well-defined checkpoints. However, many DNA damage insults are tolerated by mechanisms that can both be error-prone and error-free. The mechanisms that tolerate DNA damage and promote cell division are less well-understood. This review summarizes current information known about the checkpoint response to agents that elicit both the G2/M checkpoint and the intra-S phase checkpoint and how cells adapt to unrepaired DNA damage. Tolerance to particular bulky DNA adducts and radiomimetic agents are discussed, as well as possible mechanisms that may control phosphatases that deactivate phosphorylated proteins.

scholarly journals Coordination of DNA damage tolerance mechanisms with cell cycle progression in fission yeast

Cell Cycle ◽  
2016 ◽  
Vol 15 (2) ◽  
pp. 261-273 ◽  
Author(s):  
A. John Callegari ◽  
Thomas J. Kelly
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Fission Yeast ◽  
Cell Cycle Progression ◽  
Damage Tolerance ◽  
Tolerance Mechanisms ◽  
Dna Damage Tolerance ◽  
Cycle Progression

scholarly journals Mdt1, a Novel Rad53 FHA1 Domain-Interacting Protein, Modulates DNA Damage Tolerance and G2/M Cell Cycle Progression in Saccharomycescerevisiae

2004 ◽  
Vol 24 (7) ◽  
pp. 2779-2788 ◽  
Author(s):  
Brietta L. Pike ◽  
Suganya Yongkiettrakul ◽  
Ming-Daw Tsai ◽  
Jörg Heierhorst
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Progression ◽  
Structural Integrity ◽  
Damage Tolerance ◽  
Rna Recognition Motif ◽  
M Cell ◽  
Dna Damage Tolerance ◽  
Cycle Progression ◽  
Dependent Cell

ABSTRACT The Rad53 kinase plays a central role in yeast DNA damage checkpoints. Rad53 contains two FHA phosphothreonine-binding domains that are required for Rad53 activation and possibly downstream signaling. Here we show that the N-terminal Rad53 FHA1 domain interacts with the RNA recognition motif, coiled-coil, and SQ/TQ cluster domain-containing protein Mdt1 (YBl051C). The interaction of Rad53 and Mdt1 depends on the structural integrity of the FHA1 phosphothreonine-binding site as well as threonine-305 of Mdt1. Mdt1 is constitutively threonine phosphorylated and hyperphosphorylated in response to DNA damage in vivo. DNA damage-dependent Mdt1 hyperphosphorylation depends on the Mec1 and Tel1 checkpoint kinases, and Mec1 can directly phosphorylate a recombinant Mdt1 SQ/TQ domain fragment. MDT1 overexpression is synthetically lethal with a rad53 deletion, whereas mdt1 deletion partially suppresses the DNA damage hypersensitivity of checkpoint-compromised strains and generally improves DNA damage tolerance. In the absence of DNA damage, mdt1 deletion leads to delayed anaphase completion, with an elongated cell morphology reminiscent of that of G2/M cell cycle mutants. mdt1-dependent and DNA damage-dependent cell cycle delays are not additive, suggesting that they act in the same pathway. The data indicate that Mdt1 is involved in normal G2/M cell cycle progression and is a novel target of checkpoint-dependent cell cycle arrest pathways.

scholarly journals Schizosaccharomyces pombe Hst4 Functions in DNA Damage Response by Regulating Histone H3 K56 Acetylation

2008 ◽  
Vol 7 (5) ◽  
pp. 800-813 ◽  
Author(s):  
Devyani Haldar ◽  
Rohinton T. Kamakaka
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Schizosaccharomyces Pombe ◽  
Histone Acetylation ◽  
Dna Damage Response ◽  
Damage Tolerance ◽  
Histone H3 ◽  
S Phase ◽  
Dna Damage Tolerance ◽  
Damage Response

ABSTRACT The packaging of eukaryotic DNA into chromatin is likely to be crucial for the maintenance of genomic integrity. Histone acetylation and deacetylation, which alter chromatin accessibility, have been implicated in DNA damage tolerance. Here we show that Schizosaccharomyces pombe Hst4, a homolog of histone deacetylase Sir2, participates in S-phase-specific DNA damage tolerance. Hst4 was essential for the survival of cells exposed to the genotoxic agent methyl methanesulfonate (MMS) as well as for cells lacking components of the DNA damage checkpoint pathway. It was required for the deacetylation of histone H3 core domain residue lysine 56, since a strain with a point mutation of its catalytic domain was unable to deacetylate this residue in vivo. Hst4 regulated the acetylation of H3 K56 and was itself cell cycle regulated. We also show that MMS treatment resulted in increased acetylation of histone H3 lysine 56 in wild-type cells and hst4Δ mutants had constitutively elevated levels of histone H3 K56 acetylation. Interestingly, the level of expression of Hst4 decreased upon MMS treatment, suggesting that the cell regulates access to the site of DNA damage by changing the level of this protein. Furthermore, we find that the phenotypes of both K56Q and K56R mutants of histone H3 were similar to those of hst4Δ mutants, suggesting that proper regulation of histone acetylation is important for DNA integrity. We propose that Hst4 is a deacetylase involved in the restoration of chromatin structure following the S phase of cell cycle and DNA damage response.

scholarly journals The Chromatin-binding Protein Spn1 contributes to Genome Instability in Saccharomyces cerevisiae

2018 ◽  
Author(s):  
Alison K. Thurston ◽  
Catherine A. Radebaugh ◽  
Adam R. Almeida ◽  
Juan Lucas Argueso ◽  
Laurie A. Stargell
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Dna Damage ◽  
Genome Stability ◽  
Damage Tolerance ◽  
Genome Instability ◽  
Chromatin Binding ◽  
Dna Damage Tolerance ◽  
Template Switch

AbstractCells expend a large amount of energy to maintain their DNA sequence. DNA repair pathways, cell cycle checkpoint activation, proofreading polymerases, and chromatin structure are ways in which the cell minimizes changes to the genome. During replication, the DNA damage tolerance pathway allows the replication forks to bypass damage on the template strand. This avoids prolonged replication fork stalling, which can contribute to genome instability. The DNA damage tolerance pathway includes two sub-pathways: translesion synthesis and template switch. Post-translational modification of PCNA and the histone tails, cell cycle phase, and local DNA structure have all been shown to influence sub-pathway choice. Chromatin architecture contributes to maintaining genome stability by providing physical protection of the DNA and by regulating DNA processing pathways. As such, chromatin-binding factors have been implicated in maintaining genome stability. Using Saccharomyces cerevisiae, we examined the role of Spn1, a chromatin binding and transcription elongation factor, in DNA damage tolerance. Expression of a mutant allele of SPN1 results in increased resistance to the DNA damaging agent methyl methanesulfonate, lower spontaneous and damage-induced mutation rates, along with increased chronological lifespan. We attribute these effects to an increased usage of the template switch branch of the DNA damage tolerance pathway in the spn1 strain. This provides evidence for a role of wild type Spn1 in promoting genome instability, as well as having ties to overcoming replication stress and contributing to chronological aging.

scholarly journals Novel conserved motifs in Rev1 C-terminus are required for mutagenic DNA damage tolerance

DNA Repair ◽  
2008 ◽  
Vol 7 (9) ◽  
pp. 1455-1470 ◽  
Author(s):  
Sanjay D'Souza ◽  
Lauren S. Waters ◽  
Graham C. Walker
Keyword(s):  
Dna Damage ◽  
Damage Tolerance ◽  
Dna Damage Tolerance ◽  
Conserved Motifs ◽  
C Terminus

DNA Topoisomerases in DNA Repair and DNA Damage Tolerance

1998 ◽  
pp. 517-537 ◽  
Author(s):  
John L. Nitiss
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Damage Tolerance ◽  
Dna Damage Tolerance ◽  
Dna Topoisomerases

scholarly journals DNA-damage tolerance mediated by PCNA•Ub fusions in human cells is dependent on Rev1 but not Polη

2013 ◽  
Vol 41 (15) ◽  
pp. 7356-7369 ◽  
Author(s):  
Zhoushuai Qin ◽  
Mengxue Lu ◽  
Xin Xu ◽  
Michelle Hanna ◽  
Naoko Shiomi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Damage Tolerance ◽  
Human Cells ◽  
Dna Damage Tolerance

Deubiquitinating PCNA: a downside to DNA damage tolerance

2006 ◽  
Vol 8 (4) ◽  
pp. 303-305 ◽  
Author(s):  
Helle D. Ulrich
Keyword(s):  
Dna Damage ◽  
Damage Tolerance ◽  
Dna Damage Tolerance

DNA-Damage Tolerance

2008 ◽  
pp. 888-890
Author(s):  
Xianghong Wang
Keyword(s):  
Dna Damage ◽  
Damage Tolerance ◽  
Dna Damage Tolerance
Sign in / Sign up

Export Citation Format

Share Document