Escorcia Wilber, Forsburg Susan L
Program in Molecular & Computational Biology, University of Southern California, Los Angeles, CA 90089-2910.
Program in Molecular & Computational Biology, University of Southern California, Los Angeles, CA 90089-2910
Mol Biol Cell. 2017 Nov 1;28(22):2978-2997. doi: 10.1091/mbc.E17-02-0101. Epub 2017 Aug 30.
The replication fork protection complex (FPC) coordinates multiple processes that are crucial for unimpeded passage of the replisome through various barriers and difficult to replicate areas of the genome. We examine the function of Swi1 and Swi3, fission yeast's primary FPC components, to elucidate how replication fork stability contributes to DNA integrity in meiosis. We report that destabilization of the FPC results in reduced spore viability, delayed replication, changes in recombination, and chromosome missegregation in meiosis I and meiosis II. These phenotypes are linked to accumulation and persistence of DNA damage markers in meiosis and to problems with cohesion stability at the centromere. These findings reveal an important connection between meiotic replication fork stability and chromosome segregation, two processes with major implications to human reproductive health.
复制叉保护复合体(FPC)协调多个对复制体顺利通过基因组中的各种障碍和难以复制区域至关重要的过程。我们研究了裂殖酵母主要的FPC组分Swi1和Swi3的功能,以阐明复制叉稳定性如何在减数分裂中对DNA完整性产生影响。我们报告称,FPC的不稳定会导致孢子活力降低、复制延迟、重组变化以及减数分裂I和减数分裂II中的染色体错配。这些表型与减数分裂中DNA损伤标记物的积累和持续存在以及着丝粒处黏连稳定性问题有关。这些发现揭示了减数分裂复制叉稳定性与染色体分离之间的重要联系,这两个过程对人类生殖健康具有重大影响。