Unresolved recombination intermediates lead to ultra-fine anaphase bridges, chromosome breaks and aberrations.
Unresolved recombination intermediates lead to ultra-fine anaphase bridges, chromosome breaks and aberrations.
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DOI：
10.1038/s41556-017-0011-1
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发表时间：
2018-01
影响因子：
21.3
通讯作者：
West SC
中科院分区：
文献类型：
--
作者：
Chan YW;Fugger K;West SC
连接重组姐妹染色单体的连接分子的分离对于染色体分离是必不可少的。在这里，我们确定了未解决的重组中间体的命运，出现在GEN 1-/-敲除细胞耗尽MUS 81，两个核酸酶所需的决议。我们发现，中间体持续存在，直到有丝分裂，在那里他们形成了一个独特的后期桥，我们称之为同源重组超细桥，或HR-UFB。HR-UFB不同于复制应激相关的UFB，其出现在常见的脆性位点，并且不同于着丝粒UFB。HR-UFB由BLM解旋酶加工以产生在有丝分裂时断裂的单链RPA包被的桥。在下一个细胞周期中，DNA断裂激活DNA损伤检查点，染色体融合通过非同源末端连接产生。因此，细胞经历细胞周期延迟和大量细胞死亡。这些结果使我们提出了一个模型，详细说明了未解决的重组中间体如何促进DNA损伤和染色体不稳定性。
The resolution of joint molecules that link recombining sister chromatids is essential for chromosome segregation. Here, we determine the fate of unresolved recombination intermediates that arise in GEN1-/- knock-out cells depleted for MUS81, the two nucleases required for resolution. We find that intermediates persist until mitosis where they form a distinct class of anaphase bridges, which we term homologous recombination ultra-fine bridges, or HR-UFBs. The HR-UFBs are distinct from replication stress-associated UFBs, that arise at common fragile sites, and from centromeric UFBs. HR-UFBs are processed by BLM helicase to generate single-stranded RPA-coated bridges that are broken at mitosis. In the next cell cycle, DNA breaks activate the DNA damage checkpoint and chromosome fusions arise by non-homologous end joining. Consequently, the cells undergo a cell cycle delay and massive cell death. These results lead us to present a model detailing how unresolved recombination intermediates can promote DNA damage and chromosomal instability.
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影响因子：
16
作者：
Hodskinson, Michael R. G.;Silhan, Jan;Crossan, Gerry P.;Garaycoechea, Juan I.;Mukherjee, Shivam;Johnson, Christopher M.;Schaerer, Orlando D.;Patel, Ketan J.
通讯作者：
Patel, Ketan J.
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：
16
作者：
Chen, XB;Melchionna, R;McGowan, CH
通讯作者：
McGowan, CH
SLX1和MUS81-EME1核酸酶对Holliday连接分辨率和DNA修复的合作控制。
影响因子：
16
作者：
Castor, Dennis;Nair, Nidhi;Declais, Anne-Cecile;Lachaud, Christophe;Toth, Rachel;Macartney, Thomas J.;Lilley, David M. J.;Arthur, J. Simon C.;Rouse, John
通讯作者：
Rouse, John
影响因子：
64.5
作者：
Fekairi S;Scaglione S;Chahwan C;Taylor ER;Tissier A;Coulon S;Dong MQ;Ruse C;Yates JR 3rd;Russell P;Fuchs RP;McGowan CH;Gaillard PHL
通讯作者：
Gaillard PHL