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A Novel, Evolutionarily Conserved Gene Family with Putative Sequence-Specific Single-Stranded DNA-Binding Activity.

机译:具有推定的序列特异性单链DNA结合活性的新型,进化保守基因家族。

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摘要

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. (c)2002 Elsevier Science (USA).
机译:5q号染色体的完全和部分缺失是与侵袭性骨髓恶性肿瘤相关的复发性细胞遗传学异常。早些时候,我们在原发性白血病母细胞中的D5S672和D5S620基因座之间的5q13.3处确定了大约1.5 Mb的损失区域。白血病细胞系ML3对于5号染色体的所有区域都是二倍体,除了D5S672-D5S620区间内的反向偶联易位。在这里,我们报告细菌人工染色体(BAC)重叠群的发展,以定义断点和新基因SSBP2的鉴定,SSBP2是ML3细胞破坏的目标。初步评估SSBP2作为原发性白血病母细胞和细胞系中的抑癌基因,表明其余等位基因未经历基因内突变。 SSBP2是紧密相关,进化保守且无处不在表达的基因家族的三个成员之一。 SSBP3是鸡基因CSDP的人类直系同源基因,该基因编码序列特异性单链DNA结合蛋白。 SSBP3定位于1p31.3号染色体,第三个成员SSBP4映射至19p13.1染色体。染色体定位和推定的单链DNA结合活性表明,该家族的所有三个成员均具有通过基因剂量或其他表观遗传机制潜在的抑癌活性。 (c)2002 Elsevier Science(美国)。

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