ArticleOncogene2015
Endonuclease G initiates DNA rearrangements at the MLL breakpoint cluster upon replication stress.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Discovery of an Endonuclease G-inhibitory Ku80-peptide protecting against leukemogenic rearrangements at the MLL breakpoint cluster.Nature communications · 2026Article
- Caspase-Activated DNase localizes to cancer causing translocation breakpoints during cell differentiation.bioRxiv : the preprint server for biology · 2024Article
- Nuclear endonuclease G controls cell proliferation in ovarian cancer.FEBS open bio · 2023Article
- Apoptosis - Fueling the oncogenic fire.The FEBS journal · 2021Review
- Mutagenic Consequences of Sublethal Cell Death Signaling.International journal of molecular sciences · 2021Review
- A Fibrinogen Alpha Fragment Mitigates Chemotherapy-InducedFrontiers in oncology · 2021Article
- Vpu modulates DNA repair to suppress innate sensing and hyper-integration of HIV-1.Nature microbiology · 2020Article
- Structural adaptation of vertebrate endonuclease G for 5-hydroxymethylcytosine recognition and function.Nucleic acids research · 2020Article
- Cardiomyocyte hypertrophy induced by Endonuclease G deficiency requires reactive oxygen radicals accumulation and is inhibitable by the micropeptide humanin.Redox biology · 2018Article
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- Executioner caspases and CAD are essential for mutagenesis induced by TRAIL or vincristine.Cell death & disease · 2017Article
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- Replication stress in MLL-rearrangements.Oncoscience · 2015Article
- Leukemogenic rearrangements at the mixed lineage leukemia gene (MLL)-multiple rather than a single mechanism.Frontiers in cell and developmental biology · 2015Review
- Endonuclease G preferentially cleaves 5-hydroxymethylcytosine-modified DNA creating a substrate for recombination.Nucleic acids research · 2014Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MLL (myeloid/lymphoid or mixed-lineage leukemia) rearrangements are frequent in therapy-related and childhood acute leukemia, and are associated with poor prognosis. The majority of the rearrangements fall within a 7.3-kb MLL breakpoint cluster region (MLLbcr), particularly in a 0.4-kb hotspot at the intron11-exon12 boundary. The underlying mechanisms are poorly understood, though multiple pathways including early apoptotic signaling, accompanied by high-order DNA fragmentation, have been implicated. We introduced the MLLbcr hotspot in an EGFP-based recombination reporter system and demonstrated enhancement of both spontaneous and genotoxic treatment-induced DNA recombination by the MLLbcr in various human cell types. We identified Endonuclease G (EndoG), an apoptotic nuclease, as an essential factor for MLLbcr-specific DNA recombination after induction of replication stress. We provide evidence for replication stress-induced nuclear accumulation of EndoG, DNA binding by EndoG as well as cleavage of the chromosomal MLLbcr locus in a manner requiring EndoG. We demonstrate additional dependency of MLLbcr breakage on ATM signaling to histone H2B monoubiquitinase RNF20, involved in chromatin relaxation. Altogether our findings provide a novel mechanism underlying MLLbcr destabilization in the cells of origin of leukemogenesis, with replication stress-activated, EndoG-mediated cleavage at the MLLbcr, which may serve resolution of the stalled forks via recombination repair, however, also permits MLL rearrangements.
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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.