人們經(jīng)常在癌細(xì)胞中發(fā)現(xiàn)細(xì)胞核外染色體,。不過根據(jù)2012年1月18日發(fā)表在《自然》期刊上的一項(xiàng)研究,，美國達(dá)納法伯癌癥研究所(Dana-Farber Cancer Institute)研究人員發(fā)現(xiàn)細(xì)胞核外染色體可能在癌癥形成上也發(fā)揮著一種作用。在細(xì)胞質(zhì)中染色體被它們自己的膜包圍,，在細(xì)胞分裂期間有著較高的斷裂率和重排率,，從而潛在性地促進(jìn)癌癥轉(zhuǎn)換。
這些所謂的微核(micronuclei)一直令研究人員感到迷惑,，因?yàn)樗麄儾淮_定這些微小的細(xì)胞器是遺傳不穩(wěn)定的癌細(xì)胞產(chǎn)生的,，還是促進(jìn)癌癥形成的因子。因此這項(xiàng)研究的研究人員對(duì)這些微核進(jìn)行染色,，然后追蹤它們的細(xì)胞復(fù)制周期,。盡管細(xì)胞核染色體能夠正常復(fù)制,，但是微核要在細(xì)胞完成分裂之后較長(zhǎng)時(shí)間才繼續(xù)復(fù)制過程。因?yàn)槿旧w不是在合適的環(huán)境中復(fù)制,，所以它們經(jīng)常在微核中斷裂為較短的片段,。這些片段并不丟棄，在下一次復(fù)制周期期間會(huì)傳遞給子細(xì)胞,，并整合進(jìn)細(xì)胞核染色體中,，潛在性地促進(jìn)完整基因組發(fā)生促進(jìn)癌癥產(chǎn)生的錯(cuò)誤。
該研究論文通訊作者David Pellman說,，盡管染色體片段的錯(cuò)誤整合只發(fā)生“少數(shù)的人癌癥中,，但是我們的研究發(fā)現(xiàn)提示著它或許是一類可能更加常見的染色體損傷的一種極端例子”。(生物谷：towersimper編譯)
doi:10.1038/nature10802
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DNA breaks and chromosome pulverization from errors in mitosis
Karen Crasta, Neil J. Ganem, Regina Dagher, Alexandra B. Lantermann, Elena V. Ivanova, Yunfeng Pan, Luigi Nezi, Alexei Protopopov, Dipanjan Chowdhury & David Pellman
The involvement of whole-chromosome aneuploidy in tumorigenesis is the subject of debate, in large part because of the lack of insight into underlying mechanisms. Here we identify a mechanism by which errors in mitotic chromosome segregation generate DNA breaks via the formation of structures called micronuclei. Whole-chromosome-containing micronuclei form when mitotic errors produce lagging chromosomes. We tracked the fate of newly generated micronuclei and found that they undergo defective and asynchronous DNA replication, resulting in DNA damage and often extensive fragmentation of the chromosome in the micronucleus. Micronuclei can persist in cells over several generations but the chromosome in the micronucleus can also be distributed to daughter nuclei. Thus, chromosome segregation errors potentially lead to mutations and chromosome rearrangements that can integrate into the genome. Pulverization of chromosomes in micronuclei may also be one explanation for ‘chromothripsis’ in cancer and developmental disorders, where isolated chromosomes or chromosome arms undergo massive local DNA breakage and rearrangement.
