Sakurai Haruna
Department of Biochemistry, Faculty of Pharmaceutical Science, Setsunan University, Hirakata, Osaka, Japan.
Yakugaku Zasshi. 2011;131(10):1461-4. doi: 10.1248/yakushi.131.1461.
RecQ5 belongs to the family of RecQ DNA helicases. There are 5 RecQ homologs in mammals, and defects in 3 of them (BLM, WRN, and RECQL4) give rise to cancer predisposition syndromes in humans. Although no human disease has yet been genetically linked to a mutation in RecQ5, this enzyme is thought to have unique functions, based on its ubiquitous expression profile and specific C-terminal amino acid sequence, both of which are very different from those of other RecQ DNA helicase family members. The analysis of MEF and ES cells derived from RecQ5-deficient mice investigated by Hu et al. suggested an important role for RecQ5 in the DNA metabolism of the early embryo. However, it is unknown how RecQ5 deficiency destabilizes DNA. To address the DNA instabilities in RecQ5-deficient animals, we chose Drosophila melanogaster which has simple checkpoint systems in its syncytial embryos. By analyzing Drosophila syncytial embryos, we demonstrated that the loss of RecQ5 increased the frequency of spontaneous mitotic defects such as anaphase bridge formation. A pair of daughter nuclei that had been linked by such DNA bridges was simultaneously eliminated via a Chk2-dependent pathway. These findings suggest that the lack of RecQ5 causes spontaneous double-strand DNA breaks. RecQ5 may thus function in the resolution of anaphase DNA bridges during mitosis in syncytial embryo.
RecQ5属于RecQ DNA解旋酶家族。哺乳动物中有5种RecQ同源物，其中3种（BLM、WRN和RECQL4）的缺陷会导致人类患癌症倾向综合征。虽然尚未有人类疾病在基因上与RecQ5的突变相关联，但基于其普遍的表达谱和特定的C末端氨基酸序列，这种酶被认为具有独特的功能，这两者都与其他RecQ DNA解旋酶家族成员有很大不同。Hu等人对来自RecQ5缺陷小鼠的MEF和ES细胞进行的分析表明，RecQ5在早期胚胎的DNA代谢中起重要作用。然而，尚不清楚RecQ5缺陷如何使DNA不稳定。为了解决RecQ5缺陷动物中的DNA不稳定性问题，我们选择了黑腹果蝇，其合胞体胚胎具有简单的检查点系统。通过分析果蝇合胞体胚胎，我们证明RecQ5的缺失增加了自发有丝分裂缺陷的频率，如后期桥形成。通过Chk2依赖性途径同时消除了通过这种DNA桥连接的一对子核。这些发现表明，RecQ5的缺乏会导致自发的双链DNA断裂。因此，RecQ5可能在合胞体胚胎有丝分裂期间后期DNA桥的解决中发挥作用。
