Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.30.2 (
endonuclease
)
18,621
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Immunoglobulin heavy chain class switching has been observed in vitro. In the IgG2b-producing MPC-11 mouse myeloma cell line, IgG2a-producing cells arise at a high frequency. In some cases, switch variants producing normal-sized (Mr 55,000) gamma 2a heavy chains have arisen spontaneously from a mutagen-induced "intermediate" (ICR 9.7.1) that produces an unusually large (Mr 75,000) heavy chain. Other switch variants have been isolated directly from the parent cell line. The expressed and unexpressed gamma 2b genes of MPC-11 can be distinguished in restriction
endonuclease
digests of total genomic DNA so that DNA rearrangements detected in MPC-11 variants can be directly associated with one or the other of these two genes. We describe here DNA rearrangements occurring on the expressed heavy chain chromosome of several MPC-11 gamma 2a switch variants and on the expressed chromosome of the ICR 9.7.1 intermediate. Our data indicate that all of these variants express the parental
heavy chain variable region
(VH) gene, supporting previous protein studies. We provide mapping data for the expressed gene of both ICR 9.7.1 and one of the IgG2a-producing variant cell lines (ICR 9.9.2.1) derived from it and discuss the advantages of an in vitro switching system for examining the dynamics of the immunoglobulin heavy chain class switch.
...
PMID:DNA rearrangements in MPC-11 immunoglobulin heavy chain class-switch variants. 680 22
The genetic origin of Rheumatoid Arthritis (RA) is largely unknown. The purpose of this investigation was to assess the potential genetically determined involvement of the immunoglobulin (Ig)
heavy chain variable region
(VH) locus in the pathogenesis of RA. We tested the hypothesis of whether there is a genetic linkage between a structural abnormality of the VH gene complex and autoantibody hyperproduction in RA. We used restriction
endonuclease
generated polymorphism with human VH gene-family-specific probes to examine genomic DNA from a RA family and from unrelated RA patients from both the Tunisian and the European populations. The use of DNA samples from these ethnic origins permitted a further evaluation of the polymorphism of the human VH locus. While we found that the polymorphism of the VH locus was lower in the Tunisian population, we could not detect a restriction site polymorphism pattern restricted to RA. Together, our results do not support the involvement of major abnormalities of the Ig VH locus as a primary source in the development of RA.
...
PMID:Polymorphism of the human immunoglobulin heavy chain locus in rheumatoid arthritis. 918 12
RAG
endonuclease
initiates antibody
heavy chain variable region
exon assembly from V, D, and J segments within a chromosomal V(D)J recombination center (RC) by cleaving between paired gene segments and flanking recombination signal sequences (RSSs). The IGCR1 control region promotes DJ
H
intermediate formation by isolating Ds, J
H
s, and RCs from upstream V
H
s in a chromatin loop anchored by CTCF-binding elements (CBEs). How V
H
s access the DJ
H
RC for V
H
to DJ
H
rearrangement was unknown. We report that CBEs immediately downstream of frequently rearranged V
H
-RSSs increase recombination potential of their associated V
H
far beyond that provided by RSSs alone. This CBE activity becomes particularly striking upon IGCR1 inactivation, which allows RAG, likely via loop extrusion, to linearly scan chromatin far upstream. V
H
-associated CBEs stabilize interactions of D-proximal V
H
s first encountered by the DJ
H
RC during linear RAG scanning and thereby promote dominant rearrangement of these V
H
s by an unanticipated chromatin accessibility-enhancing CBE function.
...
PMID:CTCF-Binding Elements Mediate Accessibility of RAG Substrates During Chromatin Scanning. 2980 37
