Nuclear chromosome locations dictate segregation error frequencies.
Nuclear chromosome locations dictate segregation error frequencies.
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核染色体的位置决定了分离错误的频率。
DOI：
10.1038/s41586-022-04938-0
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发表时间：
2022-07
期刊：
影响因子：
64.8
通讯作者：
中科院分区：
文献类型：
--
作者：
细胞分裂期间的染色体分离错误产生非整倍性和微核，其可经历广泛的染色体重排，如染色体碎裂。然后选择压力形成不同的非整倍体和重排模式，例如，在癌症中，但它是未知的，是否在分离错误和微核的初始偏见存在特定的染色体。在未转化的二倍体细胞系和类器官中的易错有丝分裂后使用单细胞DNA测序，我们表明染色体具有不同的分离错误频率，导致非随机非整倍性景观。从这些细胞中分离和测序单个微核表明，错误分离的染色体也经常优先被截留在微核中。在两种癌细胞系的自然发生的微核中发现了类似的偏倚。我们发现，个别染色体的分离错误频率与它们在间期核中的位置相关，并表明这是最高的纺锤体极后的外周染色体。染色体位置的随机化、Cas9介导的实时跟踪和个体染色体的强制重新定位表明，与核中心的更大距离直接增加了错误分离的倾向。因此，癌症基因组中的染色体断裂和早期发育中的非整倍性更频繁地发生于较大的染色体，其优先位于核周边附近。我们的研究结果揭示了核染色体位置，分离错误频率和微核含量之间的直接联系，这对我们理解肿瘤基因组进化和发育过程中特定非整倍体的起源具有重要意义。在未转化的二倍体细胞系和类器官中的易错有丝分裂后使用单细胞DNA测序，显示染色体具有导致非随机非整倍性景观的不同分离错误频率。
Chromosome segregation errors during cell divisions generate aneuploidies and micronuclei, which can undergo extensive chromosomal rearrangements such as chromothripsis. Selective pressures then shape distinct aneuploidy and rearrangement patterns—for example, in cancer—but it is unknown whether initial biases in segregation errors and micronucleation exist for particular chromosomes. Using single-cell DNA sequencing after an error-prone mitosis in untransformed, diploid cell lines and organoids, we show that chromosomes have different segregation error frequencies that result in non-random aneuploidy landscapes. Isolation and sequencing of single micronuclei from these cells showed that mis-segregating chromosomes frequently also preferentially become entrapped in micronuclei. A similar bias was found in naturally occurring micronuclei of two cancer cell lines. We find that segregation error frequencies of individual chromosomes correlate with their location in the interphase nucleus, and show that this is highest for peripheral chromosomes behind spindle poles. Randomization of chromosome positions, Cas9-mediated live tracking and forced repositioning of individual chromosomes showed that a greater distance from the nuclear centre directly increases the propensity to mis-segregate. Accordingly, chromothripsis in cancer genomes and aneuploidies in early development occur more frequently for larger chromosomes, which are preferentially located near the nuclear periphery. Our findings reveal a direct link between nuclear chromosome positions, segregation error frequencies and micronucleus content, with implications for our understanding of tumour genome evolution and the origins of specific aneuploidies during development. Using single-cell DNA sequencing after an error-prone mitosis in untransformed, diploid cell lines and organoids, chromosomes are shown to have different segregation error frequencies that result in non-random aneuploidy landscapes.
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影响因子：
64.5
作者：
Davoli T;Xu AW;Mengwasser KE;Sack LM;Yoon JC;Park PJ;Elledge SJ
通讯作者：
Elledge SJ
影响因子：
64.5
作者：
Kind J;Pagie L;de Vries SS;Nahidiazar L;Dey SS;Bienko M;Zhan Y;Lajoie B;de Graaf CA;Amendola M;Fudenberg G;Imakaev M;Mirny LA;Jalink K;Dekker J;van Oudenaarden A;van Steensel B
通讯作者：
van Steensel B
影响因子：
6.4
作者：
Duijf, Pascal H. G.;Schultz, Nikolaus;Benezra, Robert
通讯作者：
Benezra, Robert
DOI：
10.1083/jcb.145.6.1119
发表时间：
1999-06-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Croft JA;Bridger JM;Boyle S;Perry P;Teague P;Bickmore WA
通讯作者：
Bickmore WA
DOI：
10.1007/978-1-0716-0664-3_9
发表时间：
2021-01-01
期刊：
CAPTURING CHROMOSOME CONFORMATION
影响因子：
--
作者：
De Luca, Kim L.;Kind, Jop
通讯作者：
Kind, Jop