Ku80 is required for addition of N nucleotides to V(D)J recombination junctions by terminal deoxynucleotidyl transferase

V(D)J recombination generates a remarkably diverse repertoire of antigen receptors through the rearrangement of germline DNA. Terminal deoxynucleotidyl transferase (TdT), a polymerase that adds random nucleotides (N regions) to recombination junctions, is a key enzyme contributing to this diversity. The current model is that TdT adds N regions during V(D)J recombination by random collision with the DNA ends, without a dependence on other cellular factors. We previously demonstrated, however, that V(D)J junctions from Ku80-deficient mice unexpectedly lack N regions, although the mechanism responsible for this effect remains undefined in the mouse system. One possibility is that junctions are formed in these mice during a stage in development when TdT is not expressed. Alternatively, Ku80 may be required for the expression, nuclear localization or enzymatic activity of TdT. Here we show that V(D)J junctions isolated from Ku80-deficient fibroblasts are devoid of N regions, as were junctions in Ku80-deficient mice. In these cells TdT protein is abundant at the time of recombination, localizes properly to the nucleus and is enzymatically active. Based on these data, we propose that TdT does not add to recombination junctions through random collision but is actively recruited to the V(D)J recombinase complex by Ku80.

Activation of αv��3-Vitronectin Binding Is a Multistage Process in which Increases in Bond Strength Are Dependent on Y747 and Y759 in the Cytoplasmic Domain of β3

Integrin receptors serve as mechanical links between the cell and its structural environment. Using αv��3 integrin expressed in K562 cells as a model system, the process by which the mechanical connection between αv��3 and vitronectin develops was analyzed by measuring the resistance of these bonds to mechanical separation. Three distinct stages of activation, as defined by increases in the αv��3-vitronectin binding strength, were defined by mutational, biochemical, and biomechanical analyses. Activation to the low binding strength stage 1 occurs through interaction with the vitronectin ligand and leads to the phosphorylation of Y747 in the β3 subunit. Stage 2 is characterized by a 4-fold increase in binding strength and is dependent on stage1 and the phosphorylation of Y747. Stage 3 is characterized by a further 2.5-fold increase in binding strength and is dependent on stage 2 events and the availability of Y759 for interaction with cellular proteins. The Y747F mutant blocked the transition from stage 1 to stage 2, and the Y759F blocked the transition from stage 2 to stage 3. The data suggest a model for tension-induced activation of αv��3 integrin.

Trachelyichthys exilis, a new species of catfish (Pisces, Auchenipteridae) from Peru / David W. Greenfield and Garrett S. Glodek.

v.72:no.3(1977)

New agnathous fishes from the Pennsylvanian of Illinois / David Bardack -- and Eugene S. Richardson, Jr. --

v.33:no.26(1977)

Morphology and relationships of saurocephalid fishes / [by] David Bardack -- and Gloria Sprinkle --.

v.16:no.12(1969)

Paracanthopterygian and acanthopterygian fishes from the Upper Cretaceous of Kansas / David Bardack --.

v.33:no.20(1976)

V. S. Khromchenko's coastal explorations in southwestern Alaska, 1822 /

v.64(1973)

Ptycholepis marshi Newberry : a chondrostean fish from the Newark group of Eastern North America / Bobb Schaeffer --, David H. Dunkle --, Nicholas G. McDonald --.

v.33:no.12(1975)

The non-therapsid reptiles of the Lufeng Basin, Yunnan, China / David Jay Simmons -- [Edited by Edward G. Nash]

v.15:no.1(1965)

Investigation of springing responses on the Great Lakes ore carrier, M/V Stewart J. Cort : final report /

"Report no. CG-D-17-81."

Sh. u-t. ʼOhole tam : v��e-hu ḥeleḳ 1 mi-sefer Tumat Yesharim/

Cover title: Tumat yesharim.

Toldot rabenu Mosheh ben Maimon : kolel ḳorot yeme ḥayav��, v��e-toldot seferav�� = Rabbi Moses ben Maimun : sein Leben und Wirken /

Title also in German: Rabbi Moses ben Maimun, geuöhnhich Rambam genanut, sein Leben und Wirken.

Geologische Beschreibung des Kantons St. Gallen und seiner umgebungen Enthalten auf Blatt IX des eidg. Atlas mit Benutzung des Nachlasses von A. Escher v. d. Linth bearb. von Reallehrer Gutzwiller, prof. Kaufmann, dr. Cas. Mösch.

Each vol. has also special t.p.