Replication stress in early S phase generates apparent micronuclei and chromosome rearrangement in fission yeast.
Replication stress in early S phase generates apparent micronuclei and chromosome rearrangement in fission yeast.
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DOI：
10.1091/mbc.e15-05-0318
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发表时间：
2015-10-01
影响因子：
3.3
通讯作者：
Forsburg SL
中科院分区：
文献类型：
--
作者：
Sabatinos SA;Ranatunga NS;Yuan JP;Green MD;Forsburg SL
由于不能完成S期，分裂酵母MCM突变体逃避有丝分裂检查点，导致非整倍体、染色体碎片和桥。真实的显示了膜结合的表观酵母微核的形成;它们产生DNA损伤信号，并可能重新加入母核。DNA复制应激导致基因组突变、重排和染色体错误分离，这些都与癌症有关。我们分析了一个分裂酵母突变体，是无法完成S期由于MCM解旋酶的缺陷亚基。尽管DNA复制不足和受损，但这些细胞逃避了G2损伤检查点，形成超细桥，片段化的着丝粒和类似微核的不均匀染色体分离。这些微核保留了DNA损伤标记，并经常与母核重新结合。存活的细胞显示出突变和染色体重排的增加率。这是第一次报告的微核样分离在酵母复制突变建立复制不足的一个重要因素，有助于检查点逃逸，异常染色体分离，染色体不稳定性。
Unable to complete S phase, a fission yeast MCM mutant evades the mitotic checkpoint, causing aneuploidy, chromosome fragments, and bridges. The formation of apparent yeast micronuclei that are membrane bound is shown in real time; they develop DNA damage signals and may rejoin the parent nucleus. DNA replication stress causes genome mutations, rearrangements, and chromosome missegregation, which are implicated in cancer. We analyze a fission yeast mutant that is unable to complete S phase due to a defective subunit of the MCM helicase. Despite underreplicated and damaged DNA, these cells evade the G2 damage checkpoint to form ultrafine bridges, fragmented centromeres, and uneven chromosome segregations that resembles micronuclei. These micronuclei retain DNA damage markers and frequently rejoin with the parent nucleus. Surviving cells show an increased rate of mutation and chromosome rearrangement. This first report of micronucleus-like segregation in a yeast replication mutant establishes underreplication as an important factor contributing to checkpoint escape, abnormal chromosome segregation, and chromosome instability.