SbcC-SbcD are the bacterial orthologs of Mre11-Rad50, a nuclease complex essential for genome stability, normal development, and viability in mammals. In vitro, these enzymes degrade long DNA palindromic structures. When inactivated along with ExoI in Escherichia coli, or Sae2 in eukaryotes, palindromic amplifications arise and propagate in cells. However, long DNA palindromes are not normally found in bacterial or human genomes, leaving the cellular substrates and function of these enzymes unknown. Here, we show that during the completion of DNA replication, convergent replication forks form a palindrome-like structural intermediate that requires nucleolytic processing by SbcC-SbcD and ExoI before chromosome replication can be completed. Inactivation of these nucleases prevents completion from occurring, and under these conditions, cells maintain viability by shunting the reaction through an aberrant recombinational pathway that leads to amplifications and instability in this region. The results identify replication completion as an event critical to maintain genome integrity and cell viability, demonstrate SbcC-SbcD-ExoI acts before RecBCD and is required to initiate the completion reaction, and reveal how defects in completion result in genomic instability.

中文翻译：

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SbcC-SbcD和ExoI处理融合叉以完成染色体复制

SbcC-SbcD是Mre11-Rad50的细菌直系同源基因，Mre11-Rad50是核酸酶复合物，对哺乳动物的基因组稳定性，正常发育和生存力至关重要。在体外，这些酶降解长的DNA回文结构。在大肠杆菌中与ExoI一起灭活时或真核生物中的Sae2，回文扩增出现并在细胞中传播。但是，在细菌或人类基因组中通常不存在长的DNA回文，因此这些酶的细胞底物和功能尚不清楚。在这里，我们显示了在DNA复制完成期间，会聚复制叉形成了回文状的结构中间体，该中间体需要在染色体复制完成之前通过SbcC-SbcD和ExoI进行核酸水解处理。这些核酸酶的失活阻止了完成的发生，并且在这些条件下，细胞通过异常的重组途径分流反应来维持活力，从而导致该区域的扩增和不稳定。结果表明复制完成是维持基因组完整性和细胞活力的关键事件，