CAJ | 학술논문

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。
FANCJ-like단백시일류ATP의뢰적5′-3′DNA해선매，삼여DNA손상수복、동원중조급G4-DNA탁해，재기인조은정성유지과정중발휘중요공능。문장계통분석료47충진핵생물적FANCJ-like단백，대기서렬결구특정급기원진화진행료심입탐토。진핵생물FANCJ-like단백포함4류성원——XPD、CHL1、RTEL1화FANCJ，단재진균적일사세계급곤충중존재엄중결실현상，여접합균문(Zygomycota)결실료 RTEL1，담자균문(Basidiomycota)화자낭균문(Ascomycota)결실료 RTEL1화 FANCJ，쌍시목곤충결실료 FANCJ。FANCJ-like 단백불부포함경전해선매공유HD1화HD2결구역，이차재HD1결구역중삽입료자신특유적Fe-S、Arch화Extra-D결구역。Fe-S화Arch결구역재4류성원중교보수，Extra-D결구역재XPD중불존재，재기타3류성원중야각불상동。재FANCJ-like단백적Fe-S、Arch화Extra-D결구역중분별발현료7개、10개화2개특유모체；제료이보도적보수모체외，HD1화HD2중분별발현료5개화12개특유모체。종저사특유모체적조성화배포래간， RTEL1화FANCJ최위상근，타문재HD2구포함량개독유모체Vb2화Vc，가능여기G4-DNA해선활성상관。진화방면적증거표명，FANCJ-like단백기원우일충HD1구삽입료Fe-S화Arch결구역적DNA해선매，재다세포진핵생물출현지전，해단백통과3차복제사건화수후적특이화과정，의차형성료목전진핵생물소포함적4류FANCJ-like단백。
The FANCJ-like 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 recombina-tion and G-quadruplex DNA unwinding, and plays a critical role in maintaining genome integrity. In this study, we systemically analyzed FNACJ-like 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-like 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 respec-tively, 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.