期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 2, 页码 349-354出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1715960114
关键词
SbcCD; Exol; Mre11; Rad50; replication completion
资金
- National Science Foundation [MCB0130486]
- National Institute of Environmental Flealth Sciences [R15ES025953]
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R15ES025953] Funding Source: NIH RePORTER
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 Exol 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 Exol 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-Exol acts before RecBCD and is required to initiate the completion reaction, and reveal how defects in completion result in genomic instability.
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