The ORC ubiquitin ligase OBI1 promotes DNA replication origin firing

Coulombe, Philippe; Nassar, Joelle; Peiffer, Isabelle; Stanojčić, Slavica; Sterkers, Yvon; Delamarre, Axel; Bocquet, Stéphane; Méchali, Marcel

doi:10.1038/s41467-019-10321-x

Cited by 31 publications

(34 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RING finger protein 219 (RNF219), containing an evolutionarily conserved RING finger domain at its N-terminus, is a poorly characterized ubiquitin ligase. A recent study shows that RNF219 is able to promote DNA replication origin firing through ubiquitination of the origin recognition complex ( Coulombe et al., 2019 ). Here, we biochemically identified RNF219 as an interacting factor of CCR4–NOT.…”

Section: Introductionmentioning

confidence: 99%

RNF219 interacts with CCR4–NOT in regulating stem cell differentiation

Chen

Wang

et al. 2020

Journal of Molecular Cell Biology

View full text Add to dashboard Cite

Regulation of RNA stability plays a crucial role in gene expression control. Deadenylation is the initial rate-limiting step for the majority of RNA decay events. Here, we show that RING finger protein 219 (RNF219) interacts with the CCR4‒NOT deadenylase complex. RNF219‒CCR4‒NOT exhibits deadenylation activity in vitro. RNA-seq analyses identify some of the 2-cell-specific genes and the neuronal genes significantly downregulated upon RNF219 knockdown, while upregulated after depletion of the CCR4‒NOT subunit CNOT10 in mouse embryonic stem (ES) cells. RNF219 depletion leads to impaired neuronal lineage commitment during ES cell differentiation. Our study suggests that RNF219 is a novel interacting partner of CCR4‒NOT and required for maintenance of ES cell pluripotency.

show abstract

Section: Introductionmentioning

confidence: 99%

RNF219 interacts with CCR4–NOT in regulating stem cell differentiation

Chen

Wang

et al. 2020

Journal of Molecular Cell Biology

View full text Add to dashboard Cite

show abstract

“…Multi-mono-ubiquitylation of ORC5 facilitates this kind of interaction, enabling opening of the local origin chromatin environment and stimulating origin activation [52].…”

Section: Discussionmentioning

confidence: 99%

Novel candidate biomarkers of origin recognition complex 1, 5 and 6 for survival surveillance in patients with hepatocellular carcinoma

Wang¹,

Wang²,

Huang³

et al. 2020

J. Cancer

View full text Add to dashboard Cite

Background: Hepatocellular carcinoma (HCC) has high morbidity and mortality and lacks effective biomarkers for early diagnosis and survival surveillance. Origin recognition complex (ORC), consisting of ORC1-6 isoforms, was examined to assess the potential significance of ORC isoforms for HCC prognosis. Methods: Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to examine differential isoform expression, stage-specific expression, calculate Pearson correlations and perform survival analysis. A human protein atlas database was utilized to evaluate the protein expression of ORCs in liver tissue. The cBioPortal database was used to assess isoform mutations and the survival significance of ORCs in HCC. Cytoscape software was employed to construct gene ontologies, metabolic pathways and gene-gene interaction networks. Results: Differential expression analysis indicated that ORC1 and ORC3-6 were highly expressed in tumor tissues in the Oncomine and GEPIA databases, while ORC2 was not. All the ORCs were showed positive and statistically significant correlations with each other (all P<0.001). ORC1-2 and ORC4-6 expressions were associated with disease stages I-IV (all P<0.05), but ORC3 was not. Survival analysis found that ORC1 and ORC4-6 expressions were associated with overall survival (OS), and ORC1-3 and ORC5-6 expression were associated with recurrence-free survival (RFS; all P<0.05). In addition, low expression of these ORC genes consistently indicated better prognosis compared with high expression. Protein expression analysis revealed that ORC1 and ORC3-6 were expressed in normal liver tissues, whereas ORC2 was not. Enrichment analysis indicated that ORCs were associated with DNA metabolic process, sequence-specific DNA binding and were involved in DNA replication, cell cycle, E2F-enabled inhibition of pre-replication complex formation and G1/S transition. Conclusions: Differentially expressed ORC1, 5 and 6 are candidate biomarkers for survival prediction and recurrence surveillance in HCC.

show abstract

“…The ubiquitin ligase activity of SHPRH could also regulate degradation of proteins involved in activation of origin firing leading to increased origin firing independent of CHK2. Recently, ubiquitin signaling pathways were shown to be involved in the regulation of origin firing [38].…”

Section: Reduced Phosphorylation Of Chk2 and Mcm2 In Cells Lacking Shprhmentioning

confidence: 99%

The Human RAD5 Homologs, HLTF and SHPRH, Have Separate Functions in DNA Damage Tolerance Dependent on the DNA Lesion Type

2020

View full text Add to dashboard Cite

Helicase-like transcription factor (HLTF) and SNF2, histone-linker, PHD and RING finger domain-containing helicase (SHPRH), the two human homologs of yeast Rad5, are believed to have a vital role in DNA damage tolerance (DDT). Here we show that HLTF, SHPRH and HLTF/SHPRH knockout cell lines show different sensitivities towards UV-irradiation, methyl methanesulfonate (MMS), cisplatin and mitomycin C (MMC), which are drugs that induce different types of DNA lesions. In general, the HLTF/SHPRH double knockout cell line was less sensitive than the single knockouts in response to all drugs, and interestingly, especially to MMS and cisplatin. Using the SupF assay, we detected an increase in the mutation frequency in HLTF knockout cells both after UV- and MMS-induced DNA lesions, while we detected a decrease in mutation frequency over UV lesions in the HLTF/SHPRH double knockout cells. No change in the mutation frequency was detected in the HLTF/SHPRH double knockout cell line after MMS treatment, even though these cells were more resistant to MMS and grew faster than the other cell lines after treatment with DNA damaging agents. This phenotype could possibly be explained by a reduced activation of checkpoint kinase 2 (CHK2) and MCM2 (a component of the pre-replication complex) after MMS treatment in cells lacking SHPRH. Our data reveal both distinct and common roles of the human RAD5 homologs dependent on the nature of DNA lesions, and identified SHPRH as a regulator of CHK2, a central player in DNA damage response.

show abstract

The ORC ubiquitin ligase OBI1 promotes DNA replication origin firing

Cited by 31 publications

References 53 publications

RNF219 interacts with CCR4–NOT in regulating stem cell differentiation

RNF219 interacts with CCR4–NOT in regulating stem cell differentiation

Novel candidate biomarkers of origin recognition complex 1, 5 and 6 for survival surveillance in patients with hepatocellular carcinoma

The Human RAD5 Homologs, HLTF and SHPRH, Have Separate Functions in DNA Damage Tolerance Dependent on the DNA Lesion Type

Contact Info

Product

Resources

About