真核生物FANCJ-like蛋白的结构与进化

Structure and evolution of the eukaryotic FANCJ-like proteins

FANCJ-like蛋白是一类ATP依赖的5′-3′DNA解旋酶,参与DNA损伤修复、同源重组及G4-DNA拆解,在基因组稳定性维持过程中发挥重要功能。文章系统分析了47种真核生物的FANCJ-like蛋白,对其序列结构特征及起源进化进行了深入探讨。真核生物FANCJ-like蛋白包含4类成员——XPD、CHL1、RTEL1和FANCJ,但在真菌的一些世系及昆虫中存在严重缺失现象,如接合菌门(Zygomycota)缺失了RTEL1,担子菌门(Basidiomycota)和子囊菌门(Ascomycota)缺失了RTEL1和FANCJ,双翅目昆虫缺失了FANCJ。FANCJ-like蛋白不仅包含经典解旋酶共有HD1和HD2结构域,而且在HD1结构域中插入了自身特有的Fe-S、Arch和Extra-D结构域。Fe-S和Arch结构域在4类成员中较保守,Extra-D结构域在XPD中不存在,在其他3类成员中也各不相同。在FANCJ-like蛋白的Fe-S、Arch和Extra-D结构域中分别发现了7个、10个和2个特有模体;除了已报道的保守模体外,HD1和HD2中分别发现了5个和12个特有模体。从这些特有模体的组成和排布来看,RTEL1和FANCJ最为相近,它们在HD2区包含两个独有模体Vb2和Vc,可能与其G4-DNA解旋活性相关。进化方面的证据表明,FANCJ-like蛋白起源于一种HD1区插入了Fe-S和Arch结构域的DNA解旋酶,在多细胞真核生物出现之前,该蛋白通过3次复制事件和随后的特异化过程,依次形成了目前真核生物所包含的4类FANCJ-like蛋白。

The FANCJ-Iike protein family is a class of ATP-dependent helicases that can catalytically unwind duplex DNA along the 5＇-3＇ direction. It is involved in the processes of DNA damage repair, homologous recombination and G-quadruplex DNA unwinding, and plays a critical role in maintaining genome integrity. In this study, we systemically analyzed FNACJ-Iike proteins from 47 eukaryotic species and discussed their sequences diversity, origin and evolution, motif organization patterns and spatial structure differences. Four members of FNACJ-like proteins,including XPD, CHL1, RTEL1 and FANCJ, were found in eukaryotes, but some of them were seriously deficient in most fungi and some insects. For example, the Zygomycota fungi lost RTEL1, Basidiomycota and Ascomycota fungi lost RTEL1 and FANCJ, and Diptera insect lost FANCJ. FANCJ-Iike proteins contain canonical motor domains HD1 and HD2, and the HD1 domain further integrates with three unique domains Fe-S, Arch and Extra-D. Fe-S and Arch domains are relatively conservative in all members of the family, but the Extra-D domain is lost in XPD and differs from one another in rest members. There are 7, 10 and 2 specific motifs found from the three unique domains respectively, while 5 and 12 specific motifs are found from HD1 and HD2 domains except the conserved motifs reported previously. By analyzing the arrangement pattern of these specific motifs, we found that RTEL1 and FANCJ are more closer and share two specific motifs Vb2 and Vc in HD2 domain, which are likely related with their G-quadruplex DNA unwinding activity. The evidence of evolution showed that FACNJ-like proteins were originated from a helicase, which has a HD1 domain inserted by extra Fe-S domain and Arch domain. By three continuous gene duplication events and followed specialization, eukaryotes finally possessed the current four members of FANCJ-like proteins.