Short-term molecular consequences of chromosome mis-segregation for genome stability.
Short-term molecular consequences of chromosome mis-segregation for genome stability.
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DOI：
10.1038/s41467-023-37095-7
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发表时间：
2023-03-11
影响因子：
16.6
通讯作者：
Santaguida, Stefano
中科院分区：
文献类型：
--
作者：
Garribba, Lorenza;De Feudis, Giuseppina;Martis, Valentino;Galli, Martina;Dumont, Marie;Eliezer, Yonatan;Wardenaar, Rene;Ippolito, Marica Rosaria;Iyer, Divya Ramalingam;Tijhuis, Andrea E.;Spierings, Diana C. J.;Schubert, Michael;Taglietti, Silvia;Soriani, Chiara;Gemble, Simon;Basto, Renata;Rhind, Nick;Foijer, Floris;Ben-David, Uri;Fachinetti, Daniele;Doksani, Ylli;Santaguida, Stefano
染色体不稳定（CIN）是基因组不稳定最常见的形式，是癌症的标志。CIN总是导致非整倍性，一种核型不平衡的状态。在这里，我们发现非整倍性也可以触发CIN。我们发现非整倍体细胞在其第一个s期经历DNA复制胁迫，并在连续的CIN状态下沉淀。这就产生了一系列具有染色体结构异常的基因多样性细胞，这些细胞要么继续增殖，要么停止分裂。循环的非整倍体细胞表现出较低的核型复杂性和DNA修复特征的表达增加。有趣的是，在高增殖的癌细胞中，相同的特征被上调，这可能使它们能够增殖，尽管非整倍体诱导的CIN带来了不利影响。总之，我们的研究揭示了非整倍体后CIN的短期起源，并表明癌细胞的非整倍体状态是基因组不稳定的点突变独立来源，为肿瘤中非整倍体的发生提供了解释。染色体不稳定导致非整倍体，一种核型不平衡的状态。通过诱导受控的染色体错误分离，Santaguida和他的同事们表明，非整倍体也可以引发染色体不稳定。
Chromosome instability (CIN) is the most common form of genome instability and is a hallmark of cancer. CIN invariably leads to aneuploidy, a state of karyotype imbalance. Here, we show that aneuploidy can also trigger CIN. We found that aneuploid cells experience DNA replication stress in their first S-phase and precipitate in a state of continuous CIN. This generates a repertoire of genetically diverse cells with structural chromosomal abnormalities that can either continue proliferating or stop dividing. Cycling aneuploid cells display lower karyotype complexity compared to the arrested ones and increased expression of DNA repair signatures. Interestingly, the same signatures are upregulated in highly-proliferative cancer cells, which might enable them to proliferate despite the disadvantage conferred by aneuploidy-induced CIN. Altogether, our study reveals the short-term origins of CIN following aneuploidy and indicates the aneuploid state of cancer cells as a point mutation-independent source of genome instability, providing an explanation for aneuploidy occurrence in tumors. Chromosomal instability leads to aneuploidy, a state of karyotype imbalance. By inducing controlled chromosome mis-segregation, Santaguida and colleagues show that aneuploidy can also instigate chromosomal instability.
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影响因子：
64.8
作者：
Burrell RA;McClelland SE;Endesfelder D;Groth P;Weller MC;Shaikh N;Domingo E;Kanu N;Dewhurst SM;Gronroos E;Chew SK;Rowan AJ;Schenk A;Sheffer M;Howell M;Kschischo M;Behrens A;Helleday T;Bartek J;Tomlinson IP;Swanton C
通讯作者：
Swanton C
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：
64.8
作者：
Cohen-Sharir Y;McFarland JM;Abdusamad M;Marquis C;Bernhard SV;Kazachkova M;Tang H;Ippolito MR;Laue K;Zerbib J;Malaby HLH;Jones A;Stautmeister LM;Bockaj I;Wardenaar R;Lyons N;Nagaraja A;Bass AJ;Spierings DCJ;Foijer F;Beroukhim R;Santaguida S;Golub TR;Stumpff J;Storchová Z;Ben-David U
通讯作者：
Ben-David U
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
64.8
作者：
Ghandi, Mahmoud;Huang, Franklin W.;Sellers, William R.
通讯作者：
Sellers, William R.