Proteins of the HORMA domain family, named for its three founding members Hop1, Rev7, and Mad2, play key roles in a broad range of eukaryotic signaling pathways, from chromosome segregation and meiotic recombination, to DNA repair, to the initiation of autophagy (1). The HORMA domain nucleates assembly of multiprotein signaling complexes by wrapping its C-terminal “safety belt” region entirely around a short, 6- to 10-amino acid “closure motif” in a binding partner, resulting in a highly stable complex (Fig. 1A). While the mechanisms governing assembly of HORMA protein signaling complexes vary, many HORMA proteins share a common disassembly pathway involving two proteins, p31^comet and the AAA+ ATPase TRIP13. p31^comet, itself a diverged HORMA protein, specifically binds HORMA proteins in their “closed” partner-bound conformation, and recruits them to TRIP13 (2⇓–4). TRIP13 partially unfolds the HORMA domain, releasing the bound closure motif and converting the substrate HORMA protein to an inactive “open” conformation poised for rebinding (5⇓⇓⇓⇓–10). This HORMA recycling pathway was first described for the spindle assembly checkpoint protein Mad2 (11⇓–13), and has since been extended to include the meiotic recombination factor Hop1 and its relatives, collectively termed meiotic HORMADs (14⇓⇓⇓⇓⇓–20). A key question has been whether TRIP13 and p31^comet regulate other HORMA protein families, including the DNA repair factor Rev7 and the autophagy regulators Atg13 and Atg101. In two recent manuscripts, Clairmont et al. (21) and Sarangi et al. (22) provide convincing evidence that TRIP13 and p31^comet regulate Rev7 function in two DNA repair pathways, and that …

中文翻译：

---

p31comet和TRIP13回收Rev7调节DNA修复[细胞生物学]

HORMA结构域家族的蛋白质以其三个创始成员Hop1，Rev7和Mad2命名，在从染色体分离和减数分裂重组到DNA修复再到自噬开始的各种真核信号通路中都起着关键作用（1）。HORMA结构域通过将其C端“安全带”区域完全包裹在结合伴侣中短的6至10个氨基酸的“封闭基序”周围，从而成核了多蛋白信号传导复合物的组装，从而形成了高度稳定的复合物（图2。 1 A）。尽管控制HORMA蛋白信号复合物装配的机制各不相同，但许多HORMA蛋白共享一个共同的拆卸途径，涉及两种蛋白，p31^彗星和AAA + ATPase TRIP13。p31^彗星，本身就是一个发散HORMA蛋白质，特异性结合在它们的“关闭”伴侣结合的构象HORMA蛋白质，并将它们募集到TRIP13（2 ⇓ - 4）。TRIP13部分展现HORMA域，释放结合的基序闭合和衬底HORMA蛋白转换为了准备重新绑定不活动“开放”的构象（5 ⇓ ⇓ ⇓ ⇓ - 10）。此HORMA再循环途径首次用于主轴描述组装检查点蛋白质的Mad2（11 ⇓ - 13），并一直延伸到包括减数分裂重组因子HOP1及其亲属，统称减数分裂HORMADs（14 ⇓。⇓ 。⇓ 。⇓ 。⇓ - 20）。一个关键的问题是TRIP13和p31^彗星是否调节其他HORMA蛋白家族，包括DNA修复因子Rev7和自噬调节剂Atg13和Atg101。在最近的两篇手稿中，Clairmont等人。（21）和Sarangi等。（22）提供了令人信服的证据，表明TRIP13和p31^彗星在两种DNA修复途径中调节Rev7的功能，并且……