Terminal deoxynucleotidyl transferases from elasmobranchs reveal structural conservation within vertebrates.
The DNA polymerase (pol) X family is an ancient group of enzymes that function in DNA replication and repair (pol beta), translesion synthesis (pol lambda and pol micro) and terminal addition of non-templated nucleotides. This latter terminal deoxynucleotidyl transferase (TdT) activity performs the unique function of providing diversity at coding joins of immunoglobulin and T-cell receptor genes. The first isolated full-length TdT genes from shark and skate are reported here. Comparisons with the three-dimensional structure of mouse TdT indicate structural similarity with elasmobranch orthologues that supports both a template-independent mode of replication and a lack of strong nucleotide bias. The vertebrate TdTs appear more closely related to pol micro and fungal polymerases than to pol lambda and pol beta. Thus, unlike other molecules of adaptive immunity, TdT is a member of an ancient gene family with a clear gene phylogeny and a high degree of similarity, which implies the existence of TdT ancestors in jawless fishes and invertebrates.
Bartl
Simona
S
Moss Landing Marine Laboratories, 8272 Moss Landing Road, CA 95039, Moss Landing, USA. sbartl@mlml.calstate.edu
Miracle
Ann L
AL
Rumfelt
Lynn L
LL
Kepler
Thomas B
TB
Mochon
Evonne
E
Litman
Gary W
GW
Flajnik
Martin F
MF
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D017124:Conserved Sequence; D004253:DNA Nucleotidylexotransferase / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D018940:Elasmobranchii / Q000235:genetics* / Q000378:metabolism; D051379:Mice / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D010802:Phylogeny; D011487:Protein Conformation; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid
D004253:DNA Nucleotidylexotransferase; D004259:DNA-Directed DNA Polymerase