Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cohesin causes replicative DNA damage by trapping DNA topological stress

ABSTRACT: DNA topological stress inhibits DNA replication fork (RF) progression and contributes to DNA replication stress. In Saccharomyces cerevisiae we demonstrate that centromeric DNA and the rDNA array are especially vulnerable to DNA topological stress during replication. The activity of the SMC complexes cohesin and condensin are linked to both the generation and repair of DNA topological stress linked damage in these regions. At cohesin enriched centromeres cohesin activity causes the accumulation of DNA damage, RF rotation and precatenation, confirming that cohesin dependent DNA topological stress impacts on normal replication progression. In contrast, at the rDNA cohesin and condensin activity inhibit the repair of damage caused by DNA topological stress. We propose that as well as generally acting to ensure faithful genetic inheritance, SMCs can disrupt genome stability by trapping DNA topological stress.

ORGANISM(S): Saccharomyces cerevisiae Schizosaccharomyces pombe

PROVIDER: GSE131558 | GEO | 2020/03/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The fork protection complex generates DNA topological stress-induced DNA damage while ensuring full and faithful genome duplication [TrAEL-seq]

Project description:The fork protection complex (FPC), composed of Mrc1, Tof1, and Csm3, supports rapid and stable DNA replication. Here, we show that FPC activity also introduces DNA damage by increasing DNA topological stress during replication. Mrc1 action increases DNA topological stress during plasmid replication, while Mrc1 or Tof1 activity causes replication stress and DNA damage within topologically constrained regions. We show that the recruitment of Top1 to the fork by Tof1 suppresses the DNA damage generated in these loci. While FPC activity introduces some DNA damage due to increased topological stress, the FPC is also necessary to prevent DNA damage in long replicons across the genome, indicating that the FPC is required for complete and faithful genome duplication. We conclude that FPC regulation must balance ensuring full genome duplication through rapid replication with minimizing the consequential DNA topological stress-induced DNA damage caused by rapid replication through constrained regions.

2024-10-21 | GSE239966 | GEO

The fork protection complex generates DNA topological stress-induced DNA damage while ensuring full and faithful genome duplication [ChIP-seq]

2024-10-21 | GSE239965 | GEO

Cohesin causes replicative DNA damage by trapping DNA topological stress

Project description:Cohesin causes replicative DNA damage by trapping DNA topological stress

| PRJNA544023 | ENA

The cohesin complex prevents Myc-induced replication stress

Project description:The cohesin complex is mutated in cancer and in a number of rare familiar syndromes collectively known as Cohesinopathies. In the latter case, cohesin deficiencies have been linked to transcriptional alterations affecting Myc and its target genes. Here, we set out to understand to what extent the role of cohesins in controlling cell cycle is dependent on Myc expression and activity. Inactivation of the cohesin complex by silencing the RAD21 subunit led to cell cycle arrest due to both transcriptional impairment of Myc target genes and alterations of replication forks, which were fewer and preferentially unidirectional. Ectopic activation of Myc in RAD21 depleted cells, fully rescued transcription and promoted S-phase entry but failed to sustain S-phase progression thus leading to a strong replicative stress response, which was associated to a robust DNA damage response, DNA damage checkpoint activation and synthetic lethality. Thus, the cohesin complex is dispensable for Myc dependent transcription but essential to prevent Myc induced replicative stress. This suggests the presence of a topological checkpoint orchestrated by cohesins that by regulating Myc level prevents S-phase entry and replicative stress in cohesion compromised cells.

2017-12-22 | GSE89799 | GEO

Comparison of genome wide binding of S. cerevisiae condensin, topo II and cohesin by ChIP

Project description:The chromosomal condensin complex gives metaphase chromosomes structural stability. In addition, condensin is required for sister chromatid resolution during their segregation in anaphase. How condensin promotes chromosome resolution is poorly understood. Chromosome segregation during anaphase also fails after inactivation of topoisomerase II (topo II), the enzyme that removes catenation between sister chromatids left behind after completion of DNA replication. This has led to the proposal that condensin promotes DNA decatenation, but direct evidence for this is missing and alternative roles for condensin in chromosome resolution have been suggested. Using the budding yeast rDNA as a model, we now show that anaphase bridges in a condensin mutant are resolved by ectopic expression of a foreign (Chlorella virus) but not endogenous topo II. This suggests that catenation prevents sister rDNA segregation, and that yeast topo II is ineffective in decatenating the locus without condensin. Condensin and topo II colocalize along both rDNA and euchromatin, consistent with coordination of their activities. We investigate the physiological consequences of condensin-dependent rDNA decatenation and find that late decatenation determines the late segregation timing of this locus during anaphase. Regulation of decatenation therefore provides a means to finetune segregation timing of chromosomes in mitosis. Keywords: ChIP-chip, Cell Cycle

2008-07-18 | GSE11988 | GEO

Replication Fork-Associated RNA-DNA Hybrids Safeguard Genomic Stability in Transcriptionally Active Regions [EdUseq]

Project description:Safeguarding replication fork stability in transcriptionally active regions, which require high DNA replication accuracy, is crucial for precise DNA replication and prevention of mutations. However, how cells ensure the stability of replication forks in these regions remains a critical challenge. Here, we discovered the pervasive existence of replication forks-associated RNA-DNA hybrids (RF-RDs) within transcriptionally active regions, where they act as a protective barrier against DNA2-mediated nascent DNA degradation and prevent replication fork collapse upon replication stress. Subsequently, the RNA helicase DDX39A dismantles RF-RDs, facilitating proper DNA2-mediated DNA resection and replication fork restart. Excessive dissolution of RF-RDs causes replication fork collapse and genomic instability, while insufficient dissolution of RF-RDs under replication stress increases fork stability, resulting in chemoresistance that can be reversed by eliminating RF-RDs. In summary, we elucidated the prevalence of RF-RDs at replication forks within transcriptionally active regions, revealed their pivotal role in safeguarding replication fork stability, and proposed that targeting RF-RDs holds promise for augmenting chemotherapeutic efficacy.

2024-12-18 | GSE281980 | GEO

Replication Fork-Associated RNA-DNA Hybrids Safeguard Genomic Stability in Transcriptionally Active Regions [WGRS]

2024-12-18 | GSE254535 | GEO

Replication Fork-Associated RNA-DNA Hybrids Safeguard Genomic Stability in Transcriptionally Active Regions [REFORC]

2024-12-18 | GSE254306 | GEO

Replication Fork-Associated RNA-DNA Hybrids Safeguard Genomic Stability in Transcriptionally Active Regions [RNA_seq]

2024-12-18 | GSE254199 | GEO

Replication Fork-Associated RNA-DNA Hybrids Safeguard Genomic Stability in Transcriptionally Active Regions [EdU_seq]

2024-12-18 | GSE254196 | GEO