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DNA damage checkpoint activation affects peptidoglycan synthesis and late divisome components in Bacillus subtilis
Molecular Microbiology ( IF 3.6 ) Pub Date : 2021-06-07 , DOI: 10.1111/mmi.14765
Emily A Masser 1 , Peter E Burby 1 , Wayne D Hawkins 1 , Brooke R Gustafson 1 , Justin S Lenhart 1 , Lyle A Simmons 1
Affiliation  

During normal DNA replication, all cells encounter damage to their genetic material. As a result, organisms have developed response pathways that provide time for the cell to complete DNA repair before cell division occurs. In Bacillus subtilis, it is well established that the SOS-induced cell division inhibitor YneA blocks cell division after genotoxic stress; however, it remains unclear how YneA enforces the checkpoint. Here, we identify mutations that disrupt YneA activity and mutations that are refractory to the YneA-induced checkpoint. We find that YneA C-terminal truncation mutants and point mutants in or near the LysM peptidoglycan binding domain render YneA incapable of checkpoint enforcement. In addition, we develop a genetic method which isolated mutations in the ftsW gene that completely bypassed checkpoint enforcement while also finding that YneA interacts with late divisome components FtsL, Pbp2b, and Pbp1. Characterization of an FtsW variant resulted in considerably shorter cells during the DNA damage response indicative of hyperactive initiation of cell division and bypass of the YneA-enforced DNA damage checkpoint. With our results, we present a model where YneA inhibits septal cell wall synthesis by binding peptidoglycan and interfering with interaction between late arriving divisome components causing DNA damage checkpoint activation.

中文翻译:

DNA 损伤检查点激活影响枯草芽孢杆菌中的肽聚糖合成和晚期分裂体成分

在正常的 DNA 复制过程中,所有细胞的遗传物质都会受到损害。因此,生物体已经开发出反应途径,为细胞在细胞分裂发生之前完成 DNA 修复提供时间。在枯草芽孢杆菌中,SOS 诱导的细胞分裂抑制剂 YneA 在基因毒性应激后阻断细胞分裂是公认的;然而,目前尚不清楚 YneA 如何执行检查点。在这里,我们确定了破坏 YneA 活性的突变和对 YneA 诱导的检查点不敏感的突变。我们发现 YneA C 末端截断突变体和 LysM 肽聚糖结合域中或附近的点突变体使 YneA 无法执行检查点。此外,我们开发了一种遗传方法,可分离ftsW中的突变完全绕过检查点执行的基因,同时还发现 YneA 与晚期分裂体成分 FtsL、Pbp2b 和 Pbp1 相互作用。FtsW 变体的表征导致 DNA 损伤反应期间的细胞相当短,这表明细胞分裂的过度启动和 YneA 强制 DNA 损伤检查点的绕过。根据我们的结果,我们提出了一个模型,其中 YneA 通过结合肽聚糖和干扰导致 DNA 损伤检查点激活的迟到的分裂体成分之间的相互作用来抑制隔膜细胞壁的合成。
更新日期:2021-06-07
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