RECQL, a member of the RecQ family of DNA helicases, suppresses chromosomal instability
RECQL, a member of the RecQ family of DNA helicases, suppresses chromosomal instability
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DOI：
10.1128/mcb.01620-06
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发表时间：
2007-03-01
影响因子：
5.3
通讯作者：
Blackshear, Perry J.
中科院分区：
文献类型：
--
作者：
Sharma, Sudha;Stumpo, Deborah J.;Blackshear, Perry J.
小鼠基因Recql是含DEx-H的DNA解旋酶的RecQ亚家族的成员。该家族的五个成员已在人类和小鼠中被鉴定，其中三个BLM、WRN和RECQL 4的突变与人类疾病和包括基因组不稳定性的细胞表型相关。迄今为止，没有人类疾病与RECQL突变相关，也没有细胞表型与其缺陷相关。为了深入了解RECQL的生理功能，我们在小鼠中破坏了Recql。与野生型小鼠相比，RECQL缺陷型小鼠没有表现出任何明显的表型差异。从RECQL缺陷小鼠胚胎成纤维细胞的细胞遗传学分析显示非整倍体，自发染色体断裂，频繁易位事件。此外，RECQL缺陷细胞对电离辐射过敏，表现出DNA损伤负荷增加，并显示自发姐妹染色单体交换升高。这些结果证明RECQL在基因组完整性所需的DNA修复过程中具有独特的细胞作用。遗传背景，功能冗余，也许其他因素可能会保护未应激小鼠从类型的异常，可能是预期从细胞水平检测到的严重的染色体畸变。
The mouse gene Recql is a member of the RecQ subfamily of DEx-H-containing DNA helicases. Five members of this family have been identified in both humans and mice, and mutations in three of these, BLM, WRN, and RECQL4, are associated with human diseases and a cellular phenotype that includes genomic instability. To date, no human disease has been associated with mutations in RECQL and no cellular phenotype has been associated with its deficiency. To gain insight into the physiological function of RECQL, we disrupted Recql in mice. RECQL-deficient mice did not exhibit any apparent phenotypic differences compared to wild-type mice. Cytogenetic analyses of embryonic fibroblasts from the RECQL-deficient mice revealed aneuploidy, spontaneous chromosomal breakage, and frequent translocation events. In addition, the RECQL-deficient cells were hypersensitive to ionizing radiation, exhibited an increased load of DNA damage, and displayed elevated spontaneous sister chromatid exchanges. These results provide evidence that RECQL has a unique cellular role in the DNA repair processes required for genomic integrity. Genetic background, functional redundancy, and perhaps other factors may protect the unstressed mouse from the types of abnormalities that might be expected from the severe chromosomal aberrations detected at the cellular level.