Chromosome Replication Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Department of Medical Biochemistry and Biophysics, Umeå University, 90187 Umeå, Sweden.
Chromosome Replication Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
Curr Biol. 2021 Jun 7;31(11):R710-R711. doi: 10.1016/j.cub.2021.03.043.
Single-stranded DNA breaks, or nicks, are amongst the most common forms of DNA damage in cells. They can be repaired by ligation; however, if a nick occurs just ahead of an approaching replisome, the outcome is a collapsed replication fork comprising a single-ended double-strand break and a 'hybrid nick' with parental DNA on one side and nascent DNA on the other (Figure 1A). We realized that in eukaryotic cells, where replication initiates from multiple replication origins, a fork from an adjacent origin can promote localized re-replication if the hybrid nick is ligated. We have modelled this situation with purified proteins in vitro and have found that there is, indeed, an additional hazard that eukaryotic replisomes face. We discuss how this problem might be mitigated.
单链 DNA 断裂，或称为缺口，是细胞中最常见的 DNA 损伤形式之一。它们可以通过连接修复；然而，如果缺口刚好出现在正在接近的复制体之前，结果将是一个崩溃的复制叉，包括一个单端双链断裂和一个“杂交缺口”，其一侧是亲本 DNA，另一侧是新生 DNA（图 1A）。我们意识到，在真核细胞中，复制从多个复制起点起始，如果杂交缺口被连接，来自相邻起点的叉可以促进局部重复制。我们已经在体外使用纯化蛋白对此情况进行了建模，并且确实发现真核复制体面临着另一个额外的危险。我们讨论了如何缓解这个问题。
