Characterization of a new BLM mutation associated with a topoisomerase II alpha defect in a patient with Bloom's syndrome
Characterization of a new BLM mutation associated with a topoisomerase II alpha defect in a patient with Bloom's syndrome
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DOI：
10.1093/hmg/6.9.1427
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发表时间：
1997-09-01
影响因子：
3.5
通讯作者：
AmorGueret, M
中科院分区：
文献类型：
--
作者：
Foucault, F;Vaury, C;AmorGueret, M
Bloom综合征（Bloom's syndrome，BS）是一种与恶性肿瘤风险增加相关的人类隐性疾病，由BLM基因的两个等位基因突变引起，BLM基因最近被鉴定为RecQ解旋酶家族的成员。BS细胞的特征是姐妹染色单体交换（SCE）速率增加，然而，在一些患者中观察到表现出正常SCE水平的淋巴细胞亚群，在本研究中，我们描述了一个BS患者中的新乌尔姆突变，该突变导致Blm的C-末端区域的高度保守的半胱氨酸被密码子1036处的苯丙氨酸取代。此外，我们的数据表明，该患者还遗传了携带影响其表达的突变的乌尔姆等位基因，并且体细胞基因内交换参与了向低SCE表型的逆转。此外，我们还表明，拓扑异构酶II α mRNA和蛋白质水平在源自该患者的高SCE细胞中均降低，而在相应的低SCE细胞中它们是正常的。总之，我们的数据使我们提出，除了其推定的解旋酶活性外，Blm还可能参与转录调节。
Bloom's syndrome (BS), a human recessive disorder associated with an increased risk of malignancy, arises through mutations in both alleles of the BLM gene, which was recently identified as a member of the RecQ helicase family, BS cells are characterized by an increased rate of sister chromatid exchange (SCE), However, a subpopulation of lymphocytes exhibiting a normal level of SCE is observed in some patients, It has been proposed that reversion to a low-SCE phenotype involves an intragenic crossing over between the paternal and maternal BLM alleles, generating a wild-type allele, In this study we characterize a new ULM mutation in a BS patient leading to the replacement, in the C-terminal region of Blm, of a highly conserved cysteine by a phenylalanine in codon 1036, Moreover, our data show that this patient also inherited a ULM allele carrying a mutation affecting its expression and that a somatic intragenic crossing over was involved in reversion to the low-SCE phenotype, Further, we show that both topoisomerase II alpha mRNA and protein levels are decreased in the high-SCE cells derived from this patient, whereas they are normal in the corresponding low-SCE cells, Altogether, our data led us to propose that besides its putative helicase activity, Blm could be involved in transcription regulation.