The N-terminal region of RECQL4 lacking the helicase domain is both essential and sufficient for the viability of vertebrate cells Role of the N-terminal region of RECQL4 in cells
The N-terminal region of RECQL4 lacking the helicase domain is both essential and sufficient for the viability of vertebrate cells Role of the N-terminal region of RECQL4 in cells
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DOI：
10.1016/j.bbamcr.2011.01.001
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发表时间：
2011-03-01
影响因子：
5.1
通讯作者：
Enomoto, Takemi
中科院分区：
文献类型：
--
作者：
Abe, Takuya;Yoshimura, Akari;Enomoto, Takemi
罗斯蒙-汤姆森综合征（RTS）是一种罕见的遗传疾病，其特征是早衰、发育异常和易患癌症。RTS是由RECQL4基因突变引起的，该基因编码人类五种RecQ解旋酶之一。为了鉴定RECQL4的细胞功能，我们建立了一个鸡DT40细胞系，在该细胞系中，强力霉素（Dox）可以关闭RECQL4的表达。暴露于Dox后，细胞停止生长并发生凋亡。RECQL4的n端区域（氨基酸1-496）缺乏解旋酶结构域，与酵母Sld2序列相似，在酿酒酵母DNA复制起始中起重要作用，可通过表达该区域拯救细胞。RECQL4 n端区域较小的片段并不能使细胞免于死亡。与RECQL4（1-496）互补的RECQL4基因敲除细胞对诱导双链断裂和交联的DNA损伤剂表现出相对较高的敏感性，这表明包括RECQL4解旋酶结构域在内的c端区域参与了某些类型DNA损伤的修复。(c) 2011 Elsevier B.V.版权所有
Rothmund-Thomson syndrome (RTS) is a rare genetic disorder characterized by premature aging, developmental abnormalities, and a predisposition to cancer. RTS is caused by mutations in the RECQL4 gene, which encodes one of the five human RecQ helicases. To identify the cellular functions of RECQL4, we generated a chicken DT40 cell line in which RECQL4 expression could be turned off by doxycycline (Dox). Upon exposure to Dox, cells stopped growing and underwent apoptosis. The cells could be rescued by expression of the N-terminal region of RECQL4 (amino acids 1-496), which lacks the helicase domain and has sequence similarity to yeast Sld2, which plays an essential function in the initiation of DNA replication in Saccharomyces cerevisiae. Smaller fragments of the N-terminal region of RECQL4 did not rescue the cells from lethality. RECQL4 gene knockout cells complemented with RECQL4 (1-496) showed relatively high sensitivity to DNA damaging agents that induce double strand breaks and cross-links, suggesting that the C-terminal region including the helicase domain of RECQL4 is involved in the repair of certain types of DNA lesions. (c) 2011 Elsevier B.V. All rights reserved.