ArticleMolecular and cellular biology2013
Both CpG methylation and activation-induced deaminase are required for the fragility of the human bcl-2 major breakpoint region: implications for the timing of the breaks in the t(14;18) translocation.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 23 citations in OpenAlex.
- Increased AID results in mutations at the CRLF2 locus implicated in Latin American ALL health disparities.Nature communications · 2024Article
- The RNA tether model for human chromosomal translocation fragile zones.Trends in biochemical sciences · 2024Review
- The mechanisms of human lymphoid chromosomal translocations and their medical relevance.Critical reviews in biochemistry and molecular biology · 2022Article
- Diversity upon diversity: linking DNA double-strand break repair to blood cancer health disparities.Trends in cancer · 2022Review
- Mechanistic basis for chromosomal translocations at the E2A gene and its broader relevance to human B cell malignancies.Cell reports · 2021Article
- The molecular basis and disease relevance of non-homologous DNA end joining.Nature reviews. Molecular cell biology · 2020Review
- Concept of DNA Lesion Longevity and Chromosomal Translocations.Trends in biochemical sciences · 2018Review
- From genetics to the clinic: a translational perspective on follicular lymphoma.Nature reviews. Cancer · 2018Review
- Teneurins: An Integrative Molecular, Functional, and Biomedical Overview of Their Role in Cancer.Frontiers in neuroscience · 2018Review
- AID and Reactive Oxygen Species Can Induce DNA Breaks within Human Chromosomal Translocation Fragile Zones.Molecular cell · 2017Article
- Physiological Roles of DNA Double-Strand Breaks.Journal of nucleic acids · 2017Review
- Mechanisms of human lymphoid chromosomal translocations.Nature reviews. Cancer · 2016Review
- Meta-Analysis of DNA Tumor-Viral Integration Site Selection Indicates a Role for Repeats, Gene Expression and Epigenetics.Cancers · 2015Article
- Methylation of CpG sites in BCL2 major breakpoint region and the increase of BCL2/JH translocation with aging.Age (Dordrecht, Netherlands) · 2015Article
- Human lymphoid translocation fragile zones are hypomethylated and have accessible chromatin.Molecular and cellular biology · 2015Article
- Production of IgG autoantibody requires expression of activation-induced deaminase in early-developing B cells in a mouse model of SLE.European journal of immunology · 2014Article
- Chromatin Memory in the Development of Human Cancers.Gene technology · 2014Article
- AID-induced remodeling of immunoglobulin genes and B cell fate.Oncotarget · 2014Review
- Article
- Regulation of immunoglobulin class-switch recombination: choreography of noncoding transcription, targeted DNA deamination, and long-range DNA repair.Advances in immunology · 2014Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
The t(14;18) chromosomal translocation typically involves breakage at the bcl-2 major breakpoint region (MBR) to cause human follicular lymphoma. A theory to explain the striking propensity of the MBR breaks at three CpG clusters within the 175-bp MBR region invoked activation-induced deaminase (AID). In a test of that theory, we used here minichromosomal substrates in human pre-B cell lines. Consistent with the essential elements of the theory, we found that the MBR breakage process is indeed highly dependent on DNA methylation at the CpG sites and highly dependent on the AID enzyme to create lesions at peak locations within the MBR. Interestingly, breakage of the phosphodiester bonds at the AID-initiated MBR lesions is RAG dependent, but, unexpectedly, most are also dependent on Artemis. We found that Artemis is capable of nicking small heteroduplex structures and is even able to nick single-base mismatches. This raises the possibility that activated Artemis, derived from the unjoined D to J(H) DNA ends at the IgH locus on chromosome 14, nicks AID-generated TG mismatches at methyl CpG sites, and this would explain why the breaks at the chromosome 18 MBR occur within the same time window as those on chromosome 14.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.