Recombination hotspot associated factors specifically recognize novel target sequences at the site of interchromosomal rearrangements in T-ALL patients with t(8;14)(q24;q11) and t(1;14)(p32;q11)

Masataka Kasai, Katsunori Aokl, Yoshinobu Matsuo, Jun Minowada, Richard Maziarz, Jack L. Strominger

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

A DNA binding protein was identified which binds to two novel target-like sequences: (I) at the 5' flanking site of the breakpoint junction of chromosome 8 in a patient with T-acute lymphoblastlc leukemla (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) rearrangement. 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 Vδ3 gene segment. In a small number of lines tested, the ReHF-1 protein was expressed in γδ lineage T cells and in a number of B cell precursor ALLs whose TCR δ locus has been rearranged. The molecular weight of ReHF-1 protein was determined to be ∼30 kDa by UV cross-linking analysis. Gel filtration chromatography and sedimentation velocity centrifugation analyses indicate that the ReHF-1 protein exists as a multimeric protein in its native form. These data might suggest a possible role for this protein in the rearrangement of the TCR δ locus. Furthermore, another protein, ReHF-2, that appears to have strict sequence specificity was found to bind only to the complementary single strand of the target sequence. The interaction of these proteins with a conserved target sequence at the chromosomal breakpoint junction might suggest that they are involved In a novel enzymatic mechanism reminiscent of the general features of DNA recombination or replication events In Escherichia coli or Saccharomyces cenvisiae.

Original languageEnglish (US)
Pages (from-to)1017-1025
Number of pages9
JournalInternational Immunology
Volume6
Issue number7
DOIs
StatePublished - Jul 1994

Fingerprint

Hot Spot
Rearrangement
Recombination
Acute
Genetic Recombination
Proteins
Protein
Target
Chromosomes
Chromosome
Locus
DNA
DNA-binding Protein
Chromosomes, Human, Pair 8
Saccharomyces
B-Lymphoid Precursor Cells
T-cells
Centrifugation
B Cells
Factors

Keywords

  • Chromosomal translocation
  • DNA binding proteins
  • TCR δ gene

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Neuropsychology and Physiological Psychology
  • Transplantation
  • Immunology

Cite this

Recombination hotspot associated factors specifically recognize novel target sequences at the site of interchromosomal rearrangements in T-ALL patients with t(8;14)(q24;q11) and t(1;14)(p32;q11). / Kasai, Masataka; Aokl, Katsunori; Matsuo, Yoshinobu; Minowada, Jun; Maziarz, Richard; Strominger, Jack L.

In: International Immunology, Vol. 6, No. 7, 07.1994, p. 1017-1025.

Research output: Contribution to journalArticle

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abstract = "A DNA binding protein was identified which binds to two novel target-like sequences: (I) at the 5' flanking site of the breakpoint junction of chromosome 8 in a patient with T-acute lymphoblastlc leukemla (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) rearrangement. 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 Vδ3 gene segment. In a small number of lines tested, the ReHF-1 protein was expressed in γδ lineage T cells and in a number of B cell precursor ALLs whose TCR δ locus has been rearranged. The molecular weight of ReHF-1 protein was determined to be ∼30 kDa by UV cross-linking analysis. Gel filtration chromatography and sedimentation velocity centrifugation analyses indicate that the ReHF-1 protein exists as a multimeric protein in its native form. These data might suggest a possible role for this protein in the rearrangement of the TCR δ locus. Furthermore, another protein, ReHF-2, that appears to have strict sequence specificity was found to bind only to the complementary single strand of the target sequence. The interaction of these proteins with a conserved target sequence at the chromosomal breakpoint junction might suggest that they are involved In a novel enzymatic mechanism reminiscent of the general features of DNA recombination or replication events In Escherichia coli or Saccharomyces cenvisiae.",
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N2 - A DNA binding protein was identified which binds to two novel target-like sequences: (I) at the 5' flanking site of the breakpoint junction of chromosome 8 in a patient with T-acute lymphoblastlc leukemla (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) rearrangement. 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 Vδ3 gene segment. In a small number of lines tested, the ReHF-1 protein was expressed in γδ lineage T cells and in a number of B cell precursor ALLs whose TCR δ locus has been rearranged. The molecular weight of ReHF-1 protein was determined to be ∼30 kDa by UV cross-linking analysis. Gel filtration chromatography and sedimentation velocity centrifugation analyses indicate that the ReHF-1 protein exists as a multimeric protein in its native form. These data might suggest a possible role for this protein in the rearrangement of the TCR δ locus. Furthermore, another protein, ReHF-2, that appears to have strict sequence specificity was found to bind only to the complementary single strand of the target sequence. The interaction of these proteins with a conserved target sequence at the chromosomal breakpoint junction might suggest that they are involved In a novel enzymatic mechanism reminiscent of the general features of DNA recombination or replication events In Escherichia coli or Saccharomyces cenvisiae.

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