TY - JOUR
T1 - V(D)J recombination in zebrafish
T2 - Normal joining products with accumulation of unresolved coding ends and deleted signal ends
AU - Li, Zhi
AU - Chang, Yung
N1 - Funding Information:
We would like to thank the DNA Laboratory at the School of Life Sciences for DNA sequencing. We thank members of Chang's lab and M. Gellert for helpful comments on the manuscript. This work was partially supported by a NIH grant (CA73857 to YC).
PY - 2007/3
Y1 - 2007/3
N2 - V(D)J recombination proceeds from a site-specific cleavage to an imprecise end joining, via generation and resolution of recombination ends. Although rearranged antigen receptor genes isolated from zebrafish (Danio rerio) resemble those made in mammals, differences may arise during evolution from lower to higher vertebrates, in regard to efficiency, fidelity and regulation of this recombination. To elucidate the V(D)J recombination reaction in zebrafish, we characterized recombination ends transiently produced by zebrafish lymphocytes, as well as joining products. Similar to their mammalian counterpart, zebrafish lymphocytes make perfect signal joints and normal coding joints, indicating their competent end resolution machinery. However, recombination ends recovered from the same zebrafish lymphoid tissues exhibit some features that are not readily seen in normal mammalian counterpart: deleted signal ends and accumulation of opened coding ends. These results indicate that the recombination reaction in zebrafish lymphocytes is inefficient and less stringently regulated, which may result from unstable post-cleavage complexes, and/or slow transition from cleavage to resolution. Our data suggests that the V(D)J recombination machinery may have undergone evolution selection to become more efficient in higher jawed vertebrates.
AB - V(D)J recombination proceeds from a site-specific cleavage to an imprecise end joining, via generation and resolution of recombination ends. Although rearranged antigen receptor genes isolated from zebrafish (Danio rerio) resemble those made in mammals, differences may arise during evolution from lower to higher vertebrates, in regard to efficiency, fidelity and regulation of this recombination. To elucidate the V(D)J recombination reaction in zebrafish, we characterized recombination ends transiently produced by zebrafish lymphocytes, as well as joining products. Similar to their mammalian counterpart, zebrafish lymphocytes make perfect signal joints and normal coding joints, indicating their competent end resolution machinery. However, recombination ends recovered from the same zebrafish lymphoid tissues exhibit some features that are not readily seen in normal mammalian counterpart: deleted signal ends and accumulation of opened coding ends. These results indicate that the recombination reaction in zebrafish lymphocytes is inefficient and less stringently regulated, which may result from unstable post-cleavage complexes, and/or slow transition from cleavage to resolution. Our data suggests that the V(D)J recombination machinery may have undergone evolution selection to become more efficient in higher jawed vertebrates.
KW - Non-homologous end joining
KW - Recombination ends
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=33751366670&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33751366670&partnerID=8YFLogxK
U2 - 10.1016/j.molimm.2006.07.295
DO - 10.1016/j.molimm.2006.07.295
M3 - Article
C2 - 17005252
AN - SCOPUS:33751366670
SN - 0161-5890
VL - 44
SP - 1793
EP - 1802
JO - Molecular Immunology
JF - Molecular Immunology
IS - 7
ER -