Functional interactions between BLM and XRCC3 in the cell.
Functional interactions between BLM and XRCC3 in the cell.
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DOI：
10.1083/jcb.200702183
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发表时间：
2007-10-08
期刊：
影响因子：
--
通讯作者：
Enomoto T
中科院分区：
文献类型：
--
作者：
Otsuki M;Seki M;Inoue E;Yoshimura A;Kato G;Yamanouchi S;Kawabe Y;Tada S;Shinohara A;Komura J;Ono T;Takeda S;Ishii Y;Enomoto T
Bloom综合征（BS）是由BLM基因突变引起的，其特征是易患多种癌症。BS细胞表现出姐妹染色单体交换（SCE）频率升高，同源染色体之间的互换（有丝分裂交叉），并对几种DNA损伤剂敏感。为了解决机制，赋予这些表型在BS细胞，我们的特点是一系列的双和三重突变体的突变BLM和其他基因参与修复途径。我们发现XRCC 3活性产生的底物导致blm细胞中SCE升高，而BLM与DNA拓扑异构酶IIIα抑制SCE的形成。此外，XRCC3活性还产生紫外线（UV）和甲磺酸甲酯（MMS）诱导的有丝分裂交叉。此外，XRCC3的破坏抑制MMS和UV敏感性以及MMS和UV诱导的blm细胞染色体畸变，表明BLM在XRCC3下游起作用。
Bloom's syndrome (BS), which is caused by mutations in the BLM gene, is characterized by a predisposition to a wide variety of cancers. BS cells exhibit elevated frequencies of sister chromatid exchanges (SCEs), interchanges between homologous chromosomes (mitotic chiasmata), and sensitivity to several DNA-damaging agents. To address the mechanism that confers these phenotypes in BS cells, we characterize a series of double and triple mutants with mutations in BLM and in other genes involved in repair pathways. We found that XRCC3 activity generates substrates that cause the elevated SCE in blm cells and that BLM with DNA topoisomerase IIIα suppresses the formation of SCE. In addition, XRCC3 activity also generates the ultraviolet (UV)- and methyl methanesulfonate (MMS)–induced mitotic chiasmata. Moreover, disruption of XRCC3 suppresses MMS and UV sensitivity and the MMS- and UV-induced chromosomal aberrations of blm cells, indicating that BLM acts downstream of XRCC3.
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