Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ABSTRACT: FIRRM/C1orf112 is synthetic lethal with PICH and mediates RAD51 dynamics

PROVIDER: PRJNA975306 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR24693220.fastq.gz	Fastqsanger.gz
	SRR24693221.fastq.gz	Fastqsanger.gz

Items per page:

1 - 2 of 2

Similar Datasets

The novel FIGNL1-interacting protein C1orf112 is synthetic lethal with ERCC6L and mediates RAD51 retention on chromatin

Project description:C1orf112 mediates RAD51 dynamics and PICH dependency

| PRJEB54793 | ENA

The FIGNL1-interacting protein C1orf112 is synthetic lethal with PICH and mediates RAD51 retention on chromatin

Project description:Joint DNA molecules are natural by-products of DNA replication and repair. Persistent joint molecules give rise to ultrafine DNA bridges (UFBs) in mitosis, which compromise sister chromatid separation. The DNA translocase PICH (ERCC6L) plays a central role in UFB resolution. To better understand the genetic context rendering cells dependent on PICH, a genome-wide loss-of-function screen was performed to identify the genetic contexts in which cells become dependent on PICH. In addition to genes involved in DNA cohesion, centromere stability and DNA damage repair, we identified the uncharacterized protein C1orf112. We find that C1orf112 interacts with and stabilizes the AAA+ ATPase FIGNL1. Inactivation of either C1orf112 or FIGNL1 resulted in UFB formation, prolonged retention of RAD51 on chromatin, impaired replication fork dynamics, and consequently impaired genome maintenance. Combined, our data reveal that inactivation of C1orf112 or FIGNL1 dysregulates RAD51 dynamics at replication forks, resulting in DNA replication defects, and a dependency on PICH to preserve cell viability.

2024-08-08 | PXD035876 | Pride

The SUMO-NIP45 pathway guards against accumulation of toxic DNA catenanes

Project description:SUMOylation is an essential protein modification that regulates numerous biological processes, but what constitutes its most critical functions in the cell remains unclear. Here, using genome-scale CRISPR-Cas9-based synthetic lethality screens, we show that the BLM-TOP3A-RMI1-RMI2 (BTRR)-PICH pathway, which resolves ultra-fine anaphase DNA bridges (UFBs) arising from catenated DNA structures, and NIP45 (NFATC2IP) display a synthetic lethal interaction in human cells and are essential for proliferation when SUMOylation is impaired. NIP45 and SUMOylation prevent excessive UFB formation that leads to extensive binucleation when BTRR-PICH-dependent UFB resolution is defective, by orchestrating an interphase pathway for converting DNA catenanes into DNA double-strand breaks that trigger G2 arrest via canonical ATM/ATR-dependent DNA damage signaling. NIP45 exerts its crucial function in this pathway by acting as a cofactor for specific SUMOylation processes that are at least in part targeted to the SLX4 multi-nuclease complex, which may facilitate nucleolytic DNA catenane resolution. Our findings establish an essential role of SUMO signaling in underpinning cell proliferation by counteracting the deleterious threat to faithful chromosome segregation posed by toxic DNA catenanes arising in virtually every cell cycle, via non-epistatic NIP45- and BTRR-PICH-dependent pathways.

2023-07-21 | PXD033739 | Pride

Cancer-associated FBXW7 loss is synthetic lethal with pharmacological targeting of CDC7

Project description:Synthetic lethal CRISPR screen in MCF10A FBXW7 isogenic models

2023-05-22 | E-MTAB-12939 | biostudies-arrayexpress

Kinome-wide shRNA screen for synthetic lethality in patient-derived FANCA-deficient fibroblasts.

Project description:The purpose of this screen was to identify synthetic lethal targets in FANCA-deficient cells.

2021-05-24 | E-MTAB-9802 | biostudies-arrayexpress

Investigating Synthetic Lethality and PARP Inhibitor Resistance in Pancreatic Cancer Through Enantiomer Differential Activity

Project description:The RAD51-BRCA2 interaction is central to DNA repair through homologous recombination. Emerging evidence indicates RAD51 overexpression and its correlation with chemoresistance in various cancers, suggesting RAD51-BRCA2 inhibition as a compelling avenue for intervention. We previously showed that combining olaparib (a PARP inhibitor (PARPi)) with RS-35d (a BRCA2-RAD51 inhibitor) was efficient in killing pancreatic ductal adenocarcinoma (PDAC) cells. However, RS-35d impaired cell viability even when administered alone, suggesting potential off-target effects. Here, through multiple, integrated orthogonal biological approaches in different 2D and 3D PDAC cultures, we characterised RS-35d enantiomers, in terms of mode of action and single contributions. By differentially inhibiting both RAD51-BRCA2 interaction and sensor kinases ATM, ATR and DNA-PK, RS-35d enantiomers exhibit a "within-pathway synthetic lethality" profile. To the best of our knowledge, this is the first reported proof-of-concept single small molecule capable of demonstrating this built-in synergism. In addition, RS-35d effect on BRCA2-mutated, olaparib-resistant PDAC cells suggests that this compound may be effective as an anticancer agent possibly capable of overcoming PARPi resistance. Our results demonstrate the potential of synthetic lethality, with its diversified applications, to propose new and concrete opportunities to effectively kill cancer cells while limiting side effects and potentially overcoming emerging drug resistance.

2025-05-07 | PXD054120 | Pride

Kinome and Rho-GTPase Synthetic Lethal shRNA Library Screen in paired NF1-/- and GAP-Related Domain Restored Schwann Cells

Project description:To identify possible novel targets for the treatment of plexiform neurofibroma formation through a synthetic lethal shRNA library screen in the tumorigenic cell of origin, Schwann cells.

2019-11-30 | E-MTAB-8398 | biostudies-arrayexpress

OCI-AML1-Cas9 EKO chemogenomic CRISPR screen

Project description:Identify genes that show synthetic lethal and synthetic recue interactions with chemical compounds

2021-03-09 | GSE157295 | GEO

OCI-AML5-Cas9 EKO chemogenomic CRISPR screen

Project description:Identify genes that show synthetic lethal and synthetic recue interactions with chemical compounds

2021-03-09 | GSE157294 | GEO

dSLAM

Project description:These datasets use diploid-based synthetic lethality analysis on microarrays (dSLAM) as a new technology for identifying genetic interactions of various types. These interactions include synthetic lethality (CIN8, BIM1, SGS1), synthetic haploinsufficiency (TUB1), dosage suppression (LCD1), suppression of a lethal mutation (SML1), suppression of an overexpressed conditionally lethal allele (CDC102), and gene-chemical interactions (Benomyl). Keywords = dSLAM yeast heterozygotes barcode tag synthetic lethality suppression Keywords: other

2004-11-05 | GSE1838 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data