UNG protects B cells from AID-induced telomere loss

Cortizas, Elena M.; Zahn, Astrid; Safavi, Sayyed Morteza; Reed, Joseph A.; Vega, Francisco; Noia, Javier M. Di; Verdún, Ramiro E.

doi:10.1084/jem.20160635

Cited by 29 publications

(35 citation statements)

References 60 publications

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“…However, as no method is available to discriminate between uracil and hmU in specific genomic regions, we do not know which SMUG1 substrate gives rise to these phenotypes in MEFs. Faithful BER of U has been shown to be needed to protect telomeres from unsolicited activation of mismatch repair at U:G pairs generated by activation-induced deaminase, leading to resection of the Crich strand in Ung À/À B cells (Cortizas et al, 2016). We could not detect expression of AID in the HAP1 cells, but we cannot exclude the possibility that AID activation at one stage during establishment of the SMUG1-KO cell line is a cause of the extremely short telomeres in this cell line.…”

Section: Discussionmentioning

confidence: 99%

SMUG1 Promotes Telomere Maintenance through Telomerase RNA Processing

et al. 2019

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Section: Discussionmentioning

confidence: 99%

SMUG1 Promotes Telomere Maintenance through Telomerase RNA Processing

et al. 2019

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“…• Extended replicative potential: Upregulation of telomerase expression, [26][27][28] and protection against AICDA off-target shortening of telomeres by the uracil-DNA glycosylase (UNG) 29 provide GC B cells with improved replicative capacity.…”

Section: G C B Cell S Inherently Fe Ature Hallmark S Of Malig Nant mentioning

confidence: 99%

Germinal center‐derived lymphomas: The darkest side of humoral immunity

Mlynarczyk

Fontán

Melnick

2019

Immunological Reviews

135

142

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Summary One of the unusual features of germinal center (GC) B cells is that they manifest many hallmarks of cancer cells. Accordingly, most B‐cell neoplasms originate from the GC reaction, and characteristically display abundant point mutations, structural genomic lesions, and clonal diversity from the genetic and epigenetic standpoints. The dominant biological theme of GC‐derived lymphomas is mutation of genes involved in epigenetic regulation and immune receptor signaling, which come into play at critical transitional stages of the GC reaction. Hence, mechanistic studies of these mutations reveal fundamental insight into the biology of the normal and malignant GC B cell. The BCL6 transcription factor plays a central role in establishing the GC phenotype in B cells, and most lymphomas are dependent on BCL6 to maintain survival, proliferation, and perhaps immune evasion. Many lymphoma mutations have the commonality of enhancing the oncogenic functions of BCL6, or overcoming some of its tumor suppressive effects. Herein, we discuss how unique features of the GC reaction create vulnerabilities that select for particular lymphoma mutations. We examine the interplay between epigenetic programming, metabolism, signaling, and immune regulatory mechanisms in lymphoma, and discuss how these are leading to novel precision therapy strategies to treat lymphoma patients.

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“…Notably, the ROS-induced DNA damage could in turn cause the generation of more ROS, resulting in a malignant injury cycle 46 . The analysis of genes downstream of TFs further demonstrated that YXS strongly activated the DNA repair system, as indicated by the elevated expression of DNA repair-related genes, such as Pen1, Pole, Eme1, Ung 47 , Dtl 48 , Ssrp1 and Mcm10 49 . Taken together, these results indicated YXS activated biological processes such as anti-apoptotic process and DNA repair to prevent H 2 O 2 -induced damage.…”

Section: Discussionmentioning

confidence: 97%

Screening and identification of critical transcription factors involved in the protection of cardiomyocytes against hydrogen peroxide-induced damage by Yixin-shu

Zhang

Geng

Guo

et al. 2017

Sci Rep

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Oxidative stress initiates harmful cellular responses, such as DNA damage and protein denaturation, triggering a series of cardiovascular disorders. Systematic investigations of the transcription factors (TFs) involved in oxidative stress can help reveal the underlying molecular mechanisms and facilitate the discovery of effective therapeutic targets in related diseases. In this study, an integrated strategy which integrated RNA-seq-based transcriptomics techniques and a newly developed concatenated tandem array of consensus TF response elements (catTFREs)-based proteomics approach and then combined with a network pharmacology analysis, was developed and this integrated strategy was used to investigate critical TFs in the protection of Yixin-shu (YXS), a standardized medical product used for ischaemic heart disease, against hydrogen peroxide (H2O2)-induced damage in cardiomyocytes. Importantly, YXS initiated biological process such as anti-apoptosis and DNA repair to protect cardiomyocytes from H2O2-induced damage. By using the integrated strategy, DNA-(apurinic or apyrimidinic site) lyase (Apex1), pre B-cell leukemia transcription factor 3 (Pbx3), and five other TFs with their functions involved in anti-oxidation, anti-apoptosis and DNA repair were identified. This study offers a new understanding of the mechanism underlying YXS-mediated protection against H2O2-induced oxidative stress in cardiomyocytes and reveals novel targets for oxidative stress-related diseases.

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UNG protects B cells from AID-induced telomere loss

Abstract: Verdun and colleagues find that the uracil-DNA glycosylase UNG, which promotes DNA breaks in the immunoglobulin genes during class switch recombination and is required for AID-induced chromosomal translocations, protects telomeres from AID-induced DNA damage and subsequent dysfunction.

Cited by 29 publications

References 60 publications

SMUG1 Promotes Telomere Maintenance through Telomerase RNA Processing

SMUG1 Promotes Telomere Maintenance through Telomerase RNA Processing

Germinal center‐derived lymphomas: The darkest side of humoral immunity

Screening and identification of critical transcription factors involved in the protection of cardiomyocytes against hydrogen peroxide-induced damage by Yixin-shu

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