Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ERCC6L2 mitigates replication stress and promotes centromere stability [Nascent_DNA_seq]

ABSTRACT: ERCC6L2 mitigates replication stress and promotes centromere stability [Nascent_DNA_seq]

PROVIDER: PRJNA939103 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR23628323_1.fastq.gz	Fastqsanger.gz
	SRR23628323_2.fastq.gz	Fastqsanger.gz
	SRR23628324_1.fastq.gz	Fastqsanger.gz
	SRR23628324_2.fastq.gz	Fastqsanger.gz
	SRR23628325_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 24

Similar Datasets

ERCC6L2 mitigates replication stress and promotes centromere stability

Project description:ERCC6L2 mitigates replication stress and promotes centromere stability

| PRJNA939098 | ENA

ERCC6L2 mitigates replication stress and promotes centromere stability [ChIP-seq]

Project description:ERCC6L2 mitigates replication stress and promotes centromere stability [ChIP-seq]

| PRJNA939100 | ENA

ERCC6L2 mitigates replication stress and promotes centromere stability [Nascent_DNA_seq]

Project description:Structurally complex genomic regions, such as centromeres, are inherently difficult to duplicate. The mechanism that underlies centromere inheritance is not well understood, and one of the key questions relates to the reassembly of centromeric chromatin following DNA replication. Here we define the SNF2 ATPase ERCC6L2 as a key regulator of this process. ERCC6L2 accumulates at centromeres and promotes efficient deposition of core centromeric factors. Our genomic analyses show that ERCC6L2 deficiency erodes centromeric chromatin, leading to unrestrained replication of centromeric DNA. We also establish that, beyond centromeres, ERCC6L2 facilitates replication at genomic repeats and non-canonical DNA structures. Notably, ERCC6L2 interacts with the major DNA replication factor PCNA through an atypical peptide, presented here as a co-crystal structure. Finally, we examine ERCC6L2 activities at DNA breaks, and show that it acts to restrict end resection independently of the 53BP1-REV7-Shieldin complex. Our observations allow us to propose a mechanistic model of ERCC6L2 activity, which reconciles its seemingly distinct functions in DNA repair and DNA replication. Together, these findings provide a new molecular context for studies linking ERCC6L2 to human disease.

2023-04-10 | GSE226154 | GEO

ERCC6L2 mitigates replication stress and promotes centromere stability [ChIP-seq]

2023-04-10 | GSE226152 | GEO

ERCC6L2 mitigates replication stress and promotes centromere stability

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-04-10 | GSE226155 | GEO

ERCC6L2 suppresses chromosome translocation

Project description:ERCC6L2 is a recently characterized component in DNA damage repair. To investigate its function in chromosome translocation, we conducted a study using K562 and HEK293T cell lines. We introduced twinned DNA double-strand breaks (DSBs) or genome-wide DSBs into these cell lines via nucleofection and transfection, respectively. Subsequently, we employed high-throughput genome translocation sequencing (HTGTS) to capture the translocation events (i.e., ligation between "prey(s)" and "bait") and the rejoining events (i.e., direct repair within the "bait" locus) under different conditions, including with or without ERCC6L2 deletion. We quantified the number of translocation events by normalizing them to the number of rejoining events, denoted as TL. Interestingly, ERCC6L2 deletion led to an increase in TL, indicating a higher frequency of translocations.

2024-11-20 | GSE281505 | GEO

H3K4 methylation at active genes mitigates transcription-replication conflicts during replication stress

Project description:H3K4 methylation at active genes mitigates transcription-replication conflicts during replication stress

| PRJNA550410 | ENA

Germline ERCC6L2 mutations lead to impaired erythropoiesis and reshaping of the bone marrow niche

Project description:Despite the inclusion of inherited myeloid malignancies as a separate entity in the WHO Classification, our understanding of the etiology of familial leukemia remains limited. ERCC6L2-deficiency is a rare, life-threatening inherited condition that gives rise to bone marrow failure (BMF), myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) resulting from germline mutations in DNA repair factor ERCC6L2. Here we employ a lentiviral shRNA approach to functionally characterize the impact of ERCC6L2 loss on hematopoietic stem/progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs). By combining cell culture assays and transcriptomic analysis of knockdown and ERCC6L2-mutated patient cells, we find that ERCC6L2-deficiency reduces HSPC clonogenic potential and delays erythropoiesis, while in MSCs it induces a significant lineage skewing, with increased osteogenesis and suppressed adipogenesis. Altogether, we demonstrate that ERCC6L2-deficiency impacts both hematopoietic and stromal compartments, and that our ex vivo model recapitulates patient phenotypes, providing a robust system to study germline mutations in hematological malignancies.

2022-09-26 | GSE190542 | GEO

DNA replication-mediated error correction of ectopic CENP-A deposition maintains centromere identity

Project description:Chromatin assembled with histone H3 variant CENP-A is the heritable epigenetic determinant of human centromere identity. Using genome-wide mapping and reference models for 23 human centromeres, CENP-A is shown in early G1 to be assembled into nucleosomes within megabase, repetitive a-satellite DNAs at each centromere and onto 11,390 sites on the chromosome arms. Centromere-bound CENP-A is found to be quantitatively maintained during DNA replication by coordinated action of the MCM2 helicase, CAF1, HJURP, and the CCAN network of constitutive centromere components. CCAN serves to tether CENP-A removed by MCM2, thereby enabling local reassembly onto both daughter centromeres with identical DNA sequence preferences and nucleosome phasing as the loading in G1 and independent of CENP-B. Conversely, without CCAN-mediated tethering, DNA replication removes CENP-A from sites on the chromosome arms. Our data identify an MCM2/CAF1/HJURP- and CCAN-dependent error correction mechanism that acts in S-phase to maintain CENP-A-dependent centromere identity.

2019-03-20 | GSE111381 | GEO

ERCC6L2 suppresses chromosome translocation

Project description:ERCC6L2 suppresses chromosome translocation

| PRJNA1184159 | ENA