All physical connections between sister chromatids must be broken before cells can divide, and eukaryotic cells have evolved multiple ways in which to process branchpoints connecting DNA molecules separated both spatially and temporally. A single DNA link between chromatids has the potential to disrupt cell cycle progression and genome integrity, so it is highly likely that cells require a nuclease that can process remaining unresolved and hemi-resolved DNA junctions and other branched species at the very late stages of mitosis. We argue that ANKLE1 probably serves this function in human cells (LEM-3 in Caenorhabditis elegans). LEM-3 has previously been shown to be located at the cell mid-body, and we show here that human ANKLE1 is a nuclease that cleaves a range of branched DNA species. It thus has the substrate selectivity consistent with an enzyme required to process a variety of unresolved and hemi-resolved branchpoints in DNA. Our results suggest that ANKLE1 acts as a catch-all enzyme of last resort that allows faithful chromosome segregation and cell division to occur.

在细胞分裂之前，姐妹染色单体之间的所有物理连接都必须被打破，真核细胞已经进化出多种方式来处理连接空间和时间上分离的 DNA 分子的分支点。染色单体之间的单个 DNA 连接有可能破坏细胞周期进程和基因组完整性，因此细胞很可能需要一种核酸酶来处理有丝分裂末期剩余的未解析和半解析的 DNA 连接以及其他分支物种。我们认为 ANKLE1 可能在人类细胞中发挥这种功能（秀丽隐杆线虫中的 LEM-3）。 LEM-3 之前已被证明位于细胞中体，我们在此表明​​人类 ANKLE1 是一种核酸酶，可以切割一系列分支 DNA 物种。因此，它具有与处理 DNA 中各种未解析和半解析分支点所需的酶一致的底物选择性。我们的结果表明，ANKLE1 充当万能酶的最后手段，允许忠实的染色体分离和细胞分裂发生。