USP28 Is Recruited to Sites of DNA Damage by the Tandem BRCT Domains of 53BP1 but Plays a Minor Role in Double-Strand Break Metabolism

Knobel, Philip A.; Belotserkovskaya, Rimma; Galanty, Yaron; Schmidt, Christine K.; Jackson, Stephen; Stracker, Travis H.

doi:10.1128/mcb.00197-14

Cited by 53 publications

(58 citation statements)

References 70 publications

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“…All three types of treatments increased the levels of H2AXS139ph when compared with the control transfected cells. As expected, UV and H 2 O 2 treatment increased the levels of the DNA repair proteins TRP53BP1 [23,24] and RAD51 [25][26][27], indicating the presence of DNA damage and supporting the use of H2AXS139ph as marker for DNA-DSB under these conditions. Interestingly, while Hmga2 transfection did not change the levels of DNA repair proteins, it increased the levels of GATA6, demonstrating a novel function of H2AXS139ph during transcriptional activation.…”

Section: Atm Is Required For Hmga2-mediated Transcriptional Activationsupporting

confidence: 76%

High mobility group protein-mediated transcription requires DNA damage marker γ-H2AX

et al. 2015

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The eukaryotic genome is organized into chromatins, the physiological template for DNA-dependent processes including replication, recombination, repair, and transcription. Chromatin-mediated transcription regulation involves DNA methylation, chromatin remodeling, and histone modifications. However, chromatin also contains non-histone chromatin-associated proteins, of which the high-mobility group (HMG) proteins are the most abundant. Although it is known that HMG proteins induce structural changes of chromatin, the processes underlying transcription regulation by HMG proteins are poorly understood. Here we decipher the molecular mechanism of transcription regulation mediated by the HMG AT-hook 2 protein (HMGA2). We combined proteomic, ChIP-seq, and transcriptome data to show that HMGA2-induced transcription requires phosphorylation of the histone variant H2AX at S139 (H2AXS139ph; γ-H2AX) mediated by the protein kinase ataxia telangiectasia mutated (ATM). Furthermore, we demonstrate the biological relevance of this mechanism within the context of TGFβ1 signaling. The interplay between HMGA2, ATM, and H2AX is a novel mechanism of transcription initiation. Our results link H2AXS139ph to transcription, assigning a new function for this DNA damage marker. Controlled chromatin opening during transcription may involve intermediates with DNA breaks that may require mechanisms that ensure the integrity of the genome.

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Section: Atm Is Required For Hmga2-mediated Transcriptional Activationsupporting

confidence: 76%

High mobility group protein-mediated transcription requires DNA damage marker γ-H2AX

et al. 2015

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“…Deletion of any component of this pathway allowed the continued proliferation of cells in the absence of centrosomes. 53BP1 interacts with p53 and is a pivotal regulator of DNA double-strand break repair, while USP28 is a deubiquitinase that interacts with 53BP1 and has a minor function in DNA damage response signaling 139–141 . However, the role of 53BP1 in responding to centrosome loss is distinct from its established role in DNA damage repair 136–138,142 .…”

Section: Sensing Centriole Numbermentioning

confidence: 99%

Once and only once: mechanisms of centriole duplication and their deregulation in disease

Nigg

Holland

2018

Nat Rev Mol Cell Biol

420

546

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Centrioles are conserved microtubule-based organelles that form the core of the centrosome and act as templates for the formation of cilia and flagella. Centrioles have important roles in most microtubule related processes, including motility, cell division and cell signaling. To coordinate these diverse cellular processes, centriole number must be tightly controlled. In cycling cells, one new centriole is formed next to each preexisting centriole in every cell cycle. Advances in imaging, proteomics, structural biology and genome editing have revealed new insights into centriole biogenesis, how centriole numbers are controlled and how alterations in these structures contribute to diseases such as cancer and neurodevelopmental disorders. Moreover, recent work has uncovered the existence of surveillance pathways that limit proliferation of cells with numerical centriole aberrations. Here we discuss recent progress in this field with a focus on signaling pathways and molecular mechanisms.

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“…USP28 was shown to bind 53BP1, but only minor DDR defects were observed in USP28-depleted cells, suggesting its minor role in DSB repair. [118]. UCH37 was reported to regulate DSB resection and repair by HR pathway through stabilizing nuclear factor related to Kappa-B-binding protein (NFRKB) [66].…”

Section: Dubs and Genomic Integritymentioning

confidence: 99%

The emerging role of deubiquitinating enzymes in genomic integrity, diseases, and therapeutics

Zhou

Shah

et al. 2016

Cell Biosci

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The addition of mono-ubiquitin or poly-ubiquitin chain to signaling proteins in response to DNA damage signal is thought to be a critical event that facilitates the recognition of DNA damage lesion site, the activation of checkpoint function, termination and checkpoint response and the recruitment of DNA repair proteins. Despite the ubiquitin modifiers, removal of ubiquitin from the functional proteins by the deubiquitinating enzymes (DUBs) plays an important role in orchestrating DNA damage response as well as DNA repair processes. Deregulated ubiquitination and deubiquitination could lead to genome instability that in turn causes tumorigenesis. Recent TCGA study has further revealed the connection between mutations in alteration of DUBs and various types of tumors. In addition, emerging drug design based on DUBs provides a new avenue for anti-cancer therapy. In this review, we will summarize the role of deubiquitination and specificity of DUBs, and highlight the recent discoveries of DUBs in the modulation of ubiquitin-mediated DNA damage response and DNA damage repair. We will furthermore discuss the DUBs involved in the tumorigenesis as well as interception of deubiquitination as a novel strategy for anti-cancer therapy.

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USP28 Is Recruited to Sites of DNA Damage by the Tandem BRCT Domains of 53BP1 but Plays a Minor Role in Double-Strand Break Metabolism

Cited by 53 publications

References 70 publications

High mobility group protein-mediated transcription requires DNA damage marker γ-H2AX

High mobility group protein-mediated transcription requires DNA damage marker γ-H2AX

Once and only once: mechanisms of centriole duplication and their deregulation in disease

The emerging role of deubiquitinating enzymes in genomic integrity, diseases, and therapeutics

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