Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

California wild mouse-derived ecotropic virus Cas-Br-M induces a spongiform encephalopathy and a wide variety of hematopoietic neoplasms on inoculation of neonatal mice. We isolated a MCF virus [Ns-6(186) MCF] from a thymic T-cell lymphoma developing in a NFS mouse inoculated with Cas-Br-M virus. Biologically cloned NS-6(186) MCF virus, in contrast to previously studied MCF viruses, was found to induce thymic or nonthymic T-cell lymphomas with high efficiency in the absence of ecotropic helper virus. Comparison of the restriction endonuclease maps derived from Cas-Br-M and NS-6(186) MCF revealed differences only in the env region, between 5.8 and 7.8 kb from the 5' end. Two biologically active molecular clones of the NS-6(186) MCF (clone 15 with two LTRs and clone 19 with 1 LTR) were studied. Although both clones exhibited similar in vitro activities, clone 15-derived virus induced only T-cell lymphomas with short latency whereas clone 19-derived virus induced a wide variety of neoplasms with a significantly longer latency. Nucleotide sequence analysis established that the U3 region of each of the two LTRs of clone 15 has a 53-bp duplication which includes "enhancer elements," but that the single LTR of clone 19 has no such duplication.
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PMID:Biologic and molecular genetic characteristics of a unique MCF virus that is highly leukemogenic in ecotropic virus-negative mice. 253 9

Histone H2AX is required to maintain genomic stability in cells and to suppress malignant transformation of lymphocytes in mice. H2ax(-/-)p53(-/-) mice succumb predominantly to immature alphabeta T-cell lymphomas with translocations, deletions, and genomic amplifications that do not involve T-cell receptor (TCR). In addition, H2ax(-/-)p53(-/-) mice also develop at lower frequencies B and T lymphomas with antigen receptor locus translocations. V(D)J recombination is initiated through the programmed induction of DNA double-strand breaks (DSBs) by the RAG1/RAG2 endonuclease. Because promiscuous RAG1/RAG2 cutting outside of antigen receptor loci can promote genomic instability, H2ax(-/-)p53(-/-) T-lineage lymphomas might arise, at least in part, through erroneous V(D)J recombination. Here, we show that H2ax(-/-)p53(-/-)Rag2(-/-) mice exhibit a similar genetic predisposition as do H2ax(-/-)p53(-/-) mice to thymic lymphoma with translocations, deletions, and amplifications. We also found that H2ax(-/-)p53(-/-)Rag2(-/-) mice often develop thymic lymphomas with loss or deletion of the p53(+) locus. Our data show that aberrant V(D)J recombination is not required for rapid onset of H2ax/p53-deficient thymic lymphomas with genomic instability and that H2ax deficiency predisposes p53(-/-)Rag2(-/-) thymocytes to transformation associated with p53 inactivation. Thus, H2AX is essential for suppressing the transformation of developing thymocytes arising from the aberrant repair of spontaneous DSBs.
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PMID:Aberrant V(D)J recombination is not required for rapid development of H2ax/p53-deficient thymic lymphomas with clonal translocations. 1904 71