RECOMBINATION HOTSPOT ASSOCIATED FACTORS SPECIFICALLY RECOGNIZE NOVELTARGET SEQUENCES AT THE SITE OF INTERCHROMOSOMAL REARRANGEMENTS IN T-ALL PATIENTS WITH T(8-14)(Q24-Q11) AND T(1-14)(P32-Q11)
M. Kasai et al., RECOMBINATION HOTSPOT ASSOCIATED FACTORS SPECIFICALLY RECOGNIZE NOVELTARGET SEQUENCES AT THE SITE OF INTERCHROMOSOMAL REARRANGEMENTS IN T-ALL PATIENTS WITH T(8-14)(Q24-Q11) AND T(1-14)(P32-Q11), International immunology, 6(7), 1994, pp. 1017-1025
A DNA binding protein was identified which binds to two novel target-l
ike sequences: (i) at the 5' flanking site of the breakpoint junction
of chromosome 8 in a patient with T-acute lymphoblastic leukemia (ALL)
carrying the t(8;14)(q24;q11) rearrangement and (ii) on chromosome 1
in three of five T-ALL patients with the t(1;14)(p32;q11) rearrangemen
t. This protein [provisionally called recombination hotspot associated
factor (ReHF-1)] was also found to bind to a similar target sequence
that is present immediately at the 3' end of the human V(delta)3 gene
segment. In a small number of lines tested, the ReHF-1 protein was exp
ressed in gammadelta lineage T cells and in a number of B cell precurs
or ALLs whose TCR delta locus has been rearranged. The molecular weigh
t of ReHF-1 protein was determined to be approximately 30 kDa by UV cr
oss-linking analysis. Gel filtration chromatography and sedimentation
velocity centrifugation analyses indicate that the ReHF-1 protein exis
ts as a multimeric protein in its native form. These data might sugges
t a possible role for this protein in the rearrangement of the TCR del
ta locus. Furthermore, another protein, ReHF-2, that appears to have s
trict sequence specificity was found to bind only to the complementary
single strand of the target sequence. The interaction of these protei
ns with a conserved target sequence at the chromosomal breakpoint junc
tion might suggest that they are involved in a novel enzymatic mechani
sm reminiscent of the general features of DNA recombination or replica
tion events in Escherichia coli or Saccharomyces cerevisiae.