Failure to complete DNA replication is one of the major sources of genome instability leading to aneuploidy, chromosome breakage, and chromosome rearrangements that are associated with human cancer. One of the surprising revelations of the past decade is that the completion of replication at so-called common fragile sites (CFS) occurs very late in the cell cycle – at mitosis – through a process termed MiDAS (mitotic DNA synthesis). MiDAS is strongly related to another cancer-promoting phenomenon: the activation of alternative lengthening of telomeres (ALT). Our understanding of the mechanisms of ALT and MiDAS in mammalian cells has drawn heavily from recent advances in the study of break-induced replication (BIR), especially in budding yeast. We provide new insights into the BIR, MiDAS, and ALT pathways and their shared similarities.

未能完成 DNA 复制是导致与人类癌症相关的非整倍体、染色体断裂和染色体重排的基因组不稳定的主要来源之一。过去十年令人惊讶的发现之一是，在所谓的常见脆弱位点 (CFS) 完成复制发生在细胞周期的很晚——有丝分裂——通过称为 MiDAS（有丝分裂 DNA 合成）的过程。MiDAS 与另一种促癌现象密切相关：端粒选择性延长 (ALT) 的激活。我们对哺乳动物细胞中 ALT 和 MiDAS 机制的理解很大程度上借鉴了断裂诱导复制 (BIR) 研究的最新进展，尤其是在出芽酵母中。我们提供了对 BIR、MiDAS 和 ALT 途径及其共同相似性的新见解。