Faculty Opinions recommendation of Replication stress links structural and numerical cancer chromosomal instability.

2013 ◽  
Author(s):  
Timothy Yen ◽  
Sanjeevani Arora
Keyword(s):  
Chromosomal Instability ◽  
Replication Stress

scholarly journals DNA-Replikationsstress, Mitose und genomische Instabilität

BIOspektrum ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 10-13
Author(s):  
Alicia Konrath ◽  
Ann-Kathrin Schmidt ◽  
Holger Bastians
Keyword(s):  
Dna Replication ◽  
Tumor Progression ◽  
Chromosome Aberrations ◽  
Chromosomal Instability ◽  
Chromosome Instability ◽  
Replication Stress ◽  
Functional Link ◽  
Structural Chromosome ◽  
Genomische Instabilität

AbstractChromosomal instability (CIN) is a hallmark of cancer and contributes to tumorigenesis and tumor progression. While structural CIN (S-CIN) leads to structural chromosome aberrations, whole chromosome instability (W-CIN) is defined by perpetual gains or losses of chromosomes during mitosis causing aneuploidy. Mitotic defects, but also abnormal DNA replication (replication stress) can lead to W-CIN. However, the functional link between replication stress, mitosis and aneuploidy is little understood.

scholarly journals Erratum: Corrigendum: Replication stress links structural and numerical cancer chromosomal instability

Nature ◽  
2013 ◽  
Vol 500 (7463) ◽  
pp. 490-490 ◽  
Author(s):  
Rebecca A. Burrell ◽  
Sarah E. McClelland ◽  
David Endesfelder ◽  
Petra Groth ◽  
Marie-Christine Weller ◽  
...  
Keyword(s):  
Chromosomal Instability ◽  
Replication Stress

scholarly journals Dormant Replication Origin Firing Links Replication Stress to Whole Chromosomal Instability in Human Cancer

2021 ◽  
Author(s):  
Ann-Kathrin Schmidt ◽  
Nicolas Böhly ◽  
Xiaoxiao Zhang ◽  
Benjamin O. Slusarenko ◽  
Magdalena Hennecke ◽  
...  
Keyword(s):  
Chromosomal Instability ◽  
Replication Origin ◽  
Human Cancer ◽  
Replication Stress ◽  
Origin Firing

scholarly journals Dormant replication origin firing links replication stress to whole chromosomal instability in human cancer

2021 ◽  
Author(s):  
Ann-Kathrin Schmidt ◽  
Nicolas Boehly ◽  
Xiaoxiao Zhang ◽  
Benjamin O. Slusarenko ◽  
Magdalena Hennecke ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Chromosomal Instability ◽  
Replication Origin ◽  
Human Cancer ◽  
Chromosome Instability ◽  
Replication Stress ◽  
S Phase ◽  
Origin Firing ◽  
Human Cancer Cells ◽  
Chromosome Missegregation

Chromosomal instability (CIN) is a hallmark of cancer and comprises structural CIN (S-CIN) and whole chromosome instability (W-CIN). Replication stress (RS), a condition of slowed or stalled DNA replication during S phase, has been linked to S-CIN, whereas defects in mitosis leading to chromosome missegregation and aneuploidy can account for W-CIN. It is well established that RS can activate additional replication origin firing that is considered as a rescue mechanism to suppress chromosomal instability in the presence of RS. In contrast, we show here that an increase in replication origin firing during S phase can contribute to W-CIN in human cancer cells. Increased origin firing can be specifically triggered by overexpression of origin firing genes including GINS1 and CDC45, whose elevated expression significantly correlates with W-CIN in human cancer specimens. Moreover, endogenous mild RS present in cancer cells characterized by W-CIN or modulation of the origin firing regulating ATR-CDK1-RIF1 axis induces dormant origin firing, which is sufficient to trigger chromosome missegregation and W-CIN. Importantly, chromosome missegregation upon increased dormant origin firing is mediated by increased microtubule growth rates leading to the generation of lagging chromosomes in mitosis, a condition prevalent in chromosomally unstable cancer cells. Thus, our study identified increased or dormant replication origin firing as a hitherto unrecognized, but cancer-relevant trigger for chromosomal instability.

scholarly journals BLM Deficiency Is Not Associated with Sensitivity to Hydroxyurea-Induced Replication Stress

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Kenza Lahkim Bennani-Belhaj ◽  
Géraldine Buhagiar-Labarchède ◽  
Nada Jmari ◽  
Rosine Onclercq-Delic ◽  
Mounira Amor-Guéret
Keyword(s):  
High Risk ◽  
Chromosomal Instability ◽  
Replication Fork ◽  
Replication Stress ◽  
Clonogenic Survival ◽  
Early Age ◽  
Replication Forks ◽  
Cellular Models ◽  
Bloom’S Syndrome ◽  
Risk Of Cancer

Bloom's syndrome (BS) displays one of the strongest known correlations between chromosomal instability and a high risk of cancer at an early age. BS cells combine a reduced average fork velocity with constitutive endogenous replication stress. However, the response of BS cells to replication stress induced by hydroxyurea (HU), which strongly slows the progression of replication forks, remains unclear due to publication of conflicting results. Using two different cellular models of BS, we showed that BLM deficiency is not associated with sensitivity to HU, in terms of clonogenic survival, DSB generation, and SCE induction. We suggest that surviving BLM-deficient cells are selected on the basis of their ability to deal with an endogenous replication stress induced by replication fork slowing, resulting in insensitivity to HU-induced replication stress.

scholarly journals Prevention of DNA Replication Stress by CHK1 Leads to Chemoresistance Despite a DNA Repair Defect in Homologous Recombination in Breast Cancer

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 238 ◽  
Author(s):  
Felix Meyer ◽  
Saskia Becker ◽  
Sandra Classen ◽  
Ann Christin Parplys ◽  
Wael Yassin Mansour ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Homologous Recombination ◽  
Triple Negative Breast Cancer ◽  
Chromosomal Instability ◽  
Triple Negative ◽  
Replication Stress ◽  
S Phase ◽  
Damage Response ◽  
Repair Defect

Chromosomal instability not only has a negative effect on survival in triple-negative breast cancer, but also on the well treatable subgroup of luminal A tumors. This suggests a general mechanism independent of subtypes. Increased chromosomal instability (CIN) in triple-negative breast cancer (TNBC) is attributed to a defect in the DNA repair pathway homologous recombination. Homologous recombination (HR) prevents genomic instability by repair and protection of replication. It is unclear whether genetic alterations actually lead to a repair defect or whether superior signaling pathways are of greater importance. Previous studies focused exclusively on the repair function of HR. Here, we show that the regulation of HR by the intra-S-phase damage response at the replication is of overriding importance. A damage response activated by Ataxia telangiectasia and Rad3 related-checkpoint kinase 1 (ATR-CHK1) can prevent replication stress and leads to resistance formation. CHK1 thus has a preferred role over HR in preventing replication stress in TNBC. The signaling cascade ATR-CHK1 can compensate for a double-strand break repair error and lead to resistance of HR-deficient tumors. Established methods for the identification of HR-deficient tumors for Poly(ADP-Ribose)-Polymerase 1 (PARP1) inhibitor therapies should be extended to include analysis of candidates for intra-S phase damage response.

scholarly journals Deficiency in Mammalian Histone H2B Ubiquitin Ligase Bre1 (Rnf20/Rnf40) Leads to Replication Stress and Chromosomal Instability

2012 ◽  
Vol 72 (8) ◽  
pp. 2111-2119 ◽  
Author(s):  
Sophia B. Chernikova ◽  
Olga V. Razorenova ◽  
John P. Higgins ◽  
Brock J. Sishc ◽  
Monica Nicolau ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Chromosomal Instability ◽  
Replication Stress ◽  
Histone H2b

scholarly journals Proteogenomic Characterization of Ovarian HGSC Implicates Mitotic Kinases, Replication Stress in Observed Chromosomal Instability

2020 ◽  
Vol 1 (5) ◽  
pp. 100075
Author(s):  
Jason E. McDermott ◽  
Osama A. Arshad ◽  
Vladislav A. Petyuk ◽  
Yi Fu ◽  
Marina A. Gritsenko ◽  
...  
Keyword(s):  
Chromosomal Instability ◽  
Replication Stress ◽  
Mitotic Kinases

scholarly journals Replication Timing and Transcription Identifies a Novel Fragility Signature Under Replication Stress

2019 ◽  
Author(s):  
Dan Sarni ◽  
Takayo Sasaki ◽  
Karin Miron ◽  
Michal Irony Tur-Sinai ◽  
Juan Carlos Rivera-Mulia ◽  
...  
Keyword(s):  
Dna Replication ◽  
Chromosomal Instability ◽  
Temporal Order ◽  
Replication Timing ◽  
Replication Stress ◽  
Fragile Sites ◽  
Precise Mapping ◽  
Chromosomal Fragility ◽  
Transcriptional Changes ◽  
Large Genes

AbstractCommon fragile sties (CFSs) are regions susceptible to replication stress and are hotspots for chromosomal instability in cancer. Several features characterizing CFSs have been associated with their instability, however, these features are prevalent across the genome and do not account for all known CFSs. Therefore, the molecular mechanism underlying CFS instability remains unclear. Here, we explored the transcriptional profile and temporal order of DNA replication (replication timing, RT) of cells under replication stress conditions. We show that the RT of only a small portion of the genome is affected by replication stress, and that CFSs are enriched for delayed RT. We identified a signature for chromosomal fragility, comprised of replication stress-induced delay in RT of early/mid S-phase replicating regions within actively transcribed large genes. This fragility signature enabled precise mapping of the core fragility region. Furthermore, the signature enabled the identification of novel fragile sites that were not detected cytogenetically, highlighting the improved sensitivity of our approach for identifying fragile sites. Altogether, this study reveals a link between altered DNA replication and transcription of large genes underlying the mechanism of CFS expression. Thus, investigating the RT and transcriptional changes in cancer may contribute to the understanding of mechanisms promoting genomic instability in cancer.

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