Mapping ubiquitination sites of S. cerevisiae Mcm10

Zhang, Tianji; Fultz, Brandy L.; Das-Bradoo, Sapna; Bielinsky, Anja‐Katrin

doi:10.1016/j.bbrep.2016.09.003

Cited by 3 publications

(4 citation statements)

References 26 publications

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“…Mcm10 is a substrate of the cullin 4 (Cul4), damaged DNA binding 1 (DDB1), viral protein R binding protein (VprBP) E3 ubiquitin ligase ( Table 1 ) [ 81 , 95 , 97 , 98 ]. These observations are consistent with the role of the cullin-RING E3 ligase family in regulating multiple cell cycle and DNA replication related proteins [ 99 ]. Although Mcm10 contains substrate recognition motifs for the anaphase promoting complex/cyclosome (APC/C), it is not an APC/C target [ 95 ].…”

Section: The Multifaceted Regulation Of Mcm10 Functionsupporting

confidence: 89%

Mcm10: A Dynamic Scaffold at Eukaryotic Replication Forks

Baxley

Bielinsky

2017

Genes

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To complete the duplication of large genomes efficiently, mechanisms have evolved that coordinate DNA unwinding with DNA synthesis and provide quality control measures prior to cell division. Minichromosome maintenance protein 10 (Mcm10) is a conserved component of the eukaryotic replisome that contributes to this process in multiple ways. Mcm10 promotes the initiation of DNA replication through direct interactions with the cell division cycle 45 (Cdc45)-minichromosome maintenance complex proteins 2-7 (Mcm2-7)-go-ichi-ni-san GINS complex proteins, as well as single- and double-stranded DNA. After origin firing, Mcm10 controls replication fork stability to support elongation, primarily facilitating Okazaki fragment synthesis through recruitment of DNA polymerase-α and proliferating cell nuclear antigen. Based on its multivalent properties, Mcm10 serves as an essential scaffold to promote DNA replication and guard against replication stress. Under pathological conditions, Mcm10 is often dysregulated. Genetic amplification and/or overexpression of MCM10 are common in cancer, and can serve as a strong prognostic marker of poor survival. These findings are compatible with a heightened requirement for Mcm10 in transformed cells to overcome limitations for DNA replication dictated by altered cell cycle control. In this review, we highlight advances in our understanding of when, where and how Mcm10 functions within the replisome to protect against barriers that cause incomplete replication.

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Section: The Multifaceted Regulation Of Mcm10 Functionsupporting

confidence: 89%

Mcm10: A Dynamic Scaffold at Eukaryotic Replication Forks

Baxley

Bielinsky

2017

Genes

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“…The loss of MCM10 is pivotal given its indispensable role in DNA replication, strand elongation [ [35] , [36] , [37] , [38] ], replication fork stability, recruitment, and binding of DNA polymerases and PCNA [ 39 ]. A collective loss in this area of the transcriptome reinforces the collapse of the replicative helicase machinery required for DNA replication and cell proliferation [ 40 ]. MCM10 is highly overexpressed in diverse human cancers and is a prognostic indicator of poor overall survival [ 41 , 42 ], advanced clinical stage, and high Gleason score [ 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Synergistic effects of methyl 2-cyano-3,11-dioxo-18beta-olean-1,-12-dien-30-oate and erlotinib on erlotinib-resistant non-small cell lung cancer cells

Nottingham

Mazzio

Surapaneni

et al. 2021

Journal of Pharmaceutical Analysis

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Non-small cell lung cancer (NSCLC) is often characterized by an underlying mutation in the epidermal growth factor receptor (EGFR), contributing to aggressive metastatic disease. Methyl 2-cyano-3,11-dioxo-18beta-olean-1,12-dien-30-oate (CDODA-Me), a glycyrrhetinic acid derivative, reportedly improves the therapeutic response to erlotinib (ERL), an EGFR tyrosine kinase inhibitor. In the present study, we performed a series of studies to demonstrate the efficacy of CDODA-Me (2 μM) in sensitizing HCC827R (ERL-resistant) cells to ERL. Herein, we first established the selectivity of ERL-induced drug resistance in the HCC827R cells, which was sensitized when ERL was combined with CDODA-Me (2 μM), shifting the IC 50 from 23.48 μM to 5.46 μM. Subsequently, whole transcriptomic microarray expression data demonstrated that the combination of ERL + CDODA-Me elicited 210 downregulated genes (0.44% of the whole transcriptome (WT)) and 174 upregulated genes (0.36% of the WT), of which approximately 80% were unique to the ERL + CDODA-Me group. Synergistic effects centered on losses to cell cycle progression transcripts, a reduction of minichromosome maintenance complex components (MCM2-7), all key components of the Cdc45·MCM2-7GINS (CMG) complex, and replicative helicases; these effects were tantamount to the upregulation of processes associated with the nuclear factor erythroid 2 like 2 translational response to oxidative stress, including sulfiredoxin 1, heme oxygenase 1, and stress-induced growth inhibitor 1. Collectively, these findings indicate that the synergistic therapeutic effects of ERL + CDODA-Me on resistant NSCLC cells are mediated via the inhibition of mitosis and induction of oxidative stress.

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“…In S. cerevisiae , MCM10 is mono‐ubiquitinated at two distinct lysine sites, subsequently, interacts with PCNA 171 . Expression level of MCM10 is precisely mediated by the CUL4 DDB1 complex 172 .…”

Section: Ptms Of Proteins Target Dna Replication and Dna Damage In Di...mentioning

confidence: 99%

“…In S. cerevisiae , MCM10 is mono‐ubiquitinated at two distinct lysine sites, subsequently, interacts with PCNA. 171 Expression level of MCM10 is precisely mediated by the CUL4 DDB1 complex. 172 De‐Ub of MCM10 results in hypersensitive to HU owing to dysregulation of the interaction between MCM10 and PCNA.…”

Section: Ptms Of Proteins Target Dna Replication and Dna Damage In Di...mentioning

confidence: 99%

DNA replication: Mechanisms and therapeutic interventions for diseases

Song

Shen

Mahasin

et al. 2023

MedComm

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Accurate and integral cellular DNA replication is modulated by multiple replication-associated proteins, which is fundamental to preserve genome stability. Furthermore, replication proteins cooperate with multiple DNA damage factors to deal with replication stress through mechanisms beyond their role in replication. Cancer cells with chronic replication stress exhibit aberrant DNA replication and DNA damage response, providing an exploitable therapeutic target in tumors. Numerous evidence has indicated that posttranslational modifications (PTMs) of replication proteins present distinct functions in DNA replication and respond to replication stress. In addition, abundant replication proteins are involved in tumorigenesis and development, which act as diagnostic and prognostic biomarkers in some tumors, implying these proteins act as therapeutic targets in clinical. Replication-target cancer therapy emerges as the times require. In this context, we outline the current investigation of the DNA replication mechanism, and simultaneously enumerate the aberrant expression of replication proteins as hallmark for various diseases, revealing their therapeutic potential for target therapy. Meanwhile, we also discuss current observations that the novel PTM of replication proteins in response to replication stress, which seems to be a promising strategy to eliminate diseases.

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Mapping ubiquitination sites of S. cerevisiae Mcm10

Cited by 3 publications

References 26 publications

Mcm10: A Dynamic Scaffold at Eukaryotic Replication Forks

Mcm10: A Dynamic Scaffold at Eukaryotic Replication Forks

Synergistic effects of methyl 2-cyano-3,11-dioxo-18beta-olean-1,-12-dien-30-oate and erlotinib on erlotinib-resistant non-small cell lung cancer cells

DNA replication: Mechanisms and therapeutic interventions for diseases

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