A novel, evolutionarily conserved gene family with putative sequence-specific single-stranded DNA-binding activity.
Complete and partial deletions of chromosome 5q are recurrent cytogenetic anomalies associated with aggressive myeloid malignancies. Earlier, we identified an approximately 1.5-Mb region of loss at 5q13.3 between the loci D5S672 and D5S620 in primary leukemic blasts. A leukemic cell line, ML3, is diploid for all of chromosome 5, except for an inversion-coupled translocation within the D5S672-D5S620 interval. Here, we report the development of a bacterial artificial chromosome (BAC) contig to define the breakpoint and the identification of a novel gene SSBP2, the target of disruption in ML3 cells. A preliminary evaluation of SSBP2 as a tumor suppressor gene in primary leukemic blasts and cell lines suggests that the remaining allele does not undergo intragenic mutations. SSBP2 is one of three members of a closely related, evolutionarily conserved, and ubiquitously expressed gene family. SSBP3 is the human ortholog of a chicken gene, CSDP, that encodes a sequence-specific single-stranded DNA-binding protein. SSBP3 localizes to chromosome 1p31.3, and the third member, SSBP4, maps to chromosome 19p13.1. Chromosomal localization and the putative single-stranded DNA-binding activity suggest that all three members of this family are capable of potential tumor suppressor activity by gene dosage or other epigenetic mechanisms.
Castro
Patricia
P
Department of Molecular Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, 77030, USA.
Liang
Hong
H
Liang
Jan C
JC
Nagarajan
Lalitha
L
D000595:Amino Acid Sequence; D022202:Chromosomes, Artificial, Bacterial; D002895:Chromosomes, Human, Pair 5; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D020161:Physical Chromosome Mapping; D016415:Sequence Alignment; D017384:Sequence Deletion; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C477058:SSBP2 protein, human