Guard the guardian: A CRL4 ligase stands watch over histone production

Lampert, Fabienne; Brodersen, Mia Mengxue Li; Peter, Matthias

doi:10.1080/19491034.2016.1276143

Cited by 6 publications

(6 citation statements)

References 56 publications

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“…The idea that CRL4 ligases are genome caretakers due to their prominent role during DNA replication and repair is not new (Lampert et al, 2017). In Arabidopsis, similar to the case of other organisms, this surveying function can be extended to other mechanisms directly related with DNA transcription.…”

Section: General Conclusion and Future Perspectivesmentioning

confidence: 99%

Arabidopsis CRL4 Complexes: Surveying Chromatin States and Gene Expression

Fonseca

Rubio

2019

Front. Plant Sci.

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CULLIN4 (CUL4) RING ligase (CRL4) complexes contain a CUL4 scaffold protein, associated to RBX1 and to DDB1 proteins and have traditionally been associated to protein degradation events. Through DDB1, these complexes can associate with numerous DCAF proteins, which directly interact with specific targets promoting their ubiquitination and subsequent degradation by the proteasome. A characteristic feature of the majority of DCAF proteins that associate with DDB1 is the presence of the DWD motif. DWD-containing proteins sum up to 85 in the plant model species Arabidopsis. In the last decade, numerous Arabidopsis DWD proteins have been studied and their molecular functions uncovered. Independently of whether their association with CRL4 has been confirmed or not, DWD proteins are often found as components of additional multimeric protein complexes that play key roles in essential nuclear events. For most of them, the significance of their complex partnership is still unexplored. Here, we summarize recent findings involving both confirmed and putative CRL4-associated DCAF proteins in regulating nuclei architecture remodelling, DNA damage repair, histone post-translational modification, mRNA processing and export, and ribosome biogenesis, that definitely have an impact in gene expression and de novo protein synthesis. We hypothesized that, by maintaining accurate levels of regulatory proteins through targeted degradation and transcriptional control, CRL4 complexes help to surveil nuclear processes essential for plant development and survival.

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Section: General Conclusion and Future Perspectivesmentioning

confidence: 99%

Arabidopsis CRL4 Complexes: Surveying Chromatin States and Gene Expression

Fonseca

Rubio

2019

Front. Plant Sci.

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“…For example, ribonucleoprotein hnRNP H/F plays a key role in binding to Gquadruplex structure in TP53 mRNA maintaining 3 0 end processing during global CpA inhibition (Decorsière et al, 2011). Additionally, the stem-loop structure formed by histone pre-mRNAs is recognized by stem-loop binding protein (SLBP) and is necessary for the 3 0 end processing of histone mRNAs (Battle & Doudna, 2001;Dominski & Marzluff, 1999;Lampert, Brodersen, & Peter, 2017;Marzluff & Koreski, 2017). More recent research has uncovered that the ubiquitin ligase CRL4, a protein complex notable for its role in genome stability (Abbas & Dutta, 2011) and UV-mediated proteolysis of cell cycle regulator p21 (Abbas et al, 2008), also monoubiquitinates SLBP, permitting proper histone mRNA 3 0 end maturation (Brodersen et al, 2016;Lampert et al, 2017).…”

Section: Competition Between Rbps and Mirnas In Controlling Gene Exmentioning

confidence: 99%

“…Additionally, the stem-loop structure formed by histone pre-mRNAs is recognized by stem-loop binding protein (SLBP) and is necessary for the 3 0 end processing of histone mRNAs (Battle & Doudna, 2001;Dominski & Marzluff, 1999;Lampert, Brodersen, & Peter, 2017;Marzluff & Koreski, 2017). More recent research has uncovered that the ubiquitin ligase CRL4, a protein complex notable for its role in genome stability (Abbas & Dutta, 2011) and UV-mediated proteolysis of cell cycle regulator p21 (Abbas et al, 2008), also monoubiquitinates SLBP, permitting proper histone mRNA 3 0 end maturation (Brodersen et al, 2016;Lampert et al, 2017). During G2 stress, cyclin-F, the substrate recognition subunit of the Skp1-Cul1-F-box E3 ligase complex, targets SLBP to proteasomal degradation and limits H2A.X signaling and apoptosis following DNA damage (Dankert et al, 2016).…”

Section: Competition Between Rbps and Mirnas In Controlling Gene Exmentioning

confidence: 99%

Connections between 3′ end processing and DNA damage response: Ten years later

Murphy

Kleiman

2019

WIREs RNA

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Ten years ago we reviewed how the cellular DNA damage response (DDR) is controlled by changes in the functional and structural properties of nuclear proteins, resulting in a timely coordinated control of gene expression that allows DNA repair. Expression of genes that play a role in DDR is regulated not only at transcriptional level during mRNA biosynthesis but also by changing steady‐state levels due to turnover of the transcripts. The 3′ end processing machinery, which is important in the regulation of mRNA stability, is involved in these gene‐specific responses to DNA damage. Here, we review the latest mechanistic connections described between 3′ end processing and DDR, with a special emphasis on alternative polyadenylation, microRNA and RNA binding proteins‐mediated deadenylation, and discuss the implications of deregulation of these steps in DDR and human disease. This article is categorized under: RNA Processing > 3′ End Processing RNA‐Based Catalysis > Miscellaneous RNA‐Catalyzed Reactions RNA in Disease and Development > RNA in Disease

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“…Loss of CUL-4 could affect localization or function in a number of different proteins important for DSB formation. Another possibility is that DSB formation defects stem from CUL-4’s effect on chromosomal structure, since CUL-4 is known to ubiquitinate histones in humans and mice (discussed in: [85]). Our analysis also demonstrated that dysfunctional CRL4 can interfere with the repression of the Tc3 transposase.…”

Section: Discussionmentioning

confidence: 99%

CRL4 regulates recombination and synaptonemal complex aggregation in the Caenorhabditis elegans germline

et al. 2019

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To maintain the integrity of the genome, meiotic DNA double strand breaks (DSBs) need to form by the meiosis-specific nuclease Spo11 and be repaired by homologous recombination. One class of products formed by recombination are crossovers, which are required for proper chromosome segregation in the first meiotic division. The synaptonemal complex (SC) is a protein structure that connects homologous chromosomes during meiotic prophase I. The proper assembly of the SC is important for recombination, crossover formation, and the subsequent chromosome segregation. Here we identify the components of Cullin RING E3 ubiquitin ligase 4 (CRL4) that play a role in SC assembly in Caenorhabditis elegans. Mutants of the CRL4 complex (cul-4, ddb-1, and gad-1) show defects in SC assembly manifested in the formation of polycomplexes (PCs), impaired progression of meiotic recombination, and reduction in crossover numbers. PCs that are formed in cul-4 mutants lack the mobile properties of wild type SC, but are likely not a direct target of ubiquitination. In C. elegans, SC assembly does not require recombination and there is no evidence that PC formation is regulated by recombination as well. However, in one cul-4 mutant PC formation is dependent upon early meiotic recombination, indicating that proper assembly of the SC can be diminished by recombination in some scenarios. Lastly, our studies suggest that CUL-4 deregulation leads to transposition of the Tc3 transposable element, and defects in formation of SPO-11-mediated DSBs. Our studies highlight previously unknown functions of CRL4 in C. elegans meiosis and show that CUL-4 likely plays multiple roles in meiosis that are essential for maintaining genome integrity.

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Guard the guardian: A CRL4 ligase stands watch over histone production

Cited by 6 publications

References 56 publications

Arabidopsis CRL4 Complexes: Surveying Chromatin States and Gene Expression

Arabidopsis CRL4 Complexes: Surveying Chromatin States and Gene Expression

Connections between 3′ end processing and DNA damage response: Ten years later

CRL4 regulates recombination and synaptonemal complex aggregation in the Caenorhabditis elegans germline

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