The cohesin modifier ESCO2 is stable during DNA replication.
The cohesin modifier ESCO2 is stable during DNA replication.
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DOI：
10.1007/s10577-023-09711-1
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发表时间：
2023-01-28
影响因子：
2.6
通讯作者：
Rankin, Susannah
中科院分区：
文献类型：
--
作者：
Jevitt, Allison M. M.;Rankin, Brooke D. D.;Chen, Jingrong;Rankin, Susannah
通过粘连蛋白复合物在姐妹染色单体之间的粘连确保了染色体的精确分离，并使重组DNA修复成为可能。通过ESCO 2乙酰转移酶乙酰化粘附素的SMC 3亚基，抑制粘附素从染色质释放，促进姐妹染色单体的粘附。ESCO 2与DNA复制机制的相互作用，部分通过ESCO 2中的PCNA相互作用蛋白（PIP）基序，是完全建立内聚所必需的。最近的报道表明，Cul 4依赖性降解调节复制后ESCO 2蛋白的水平。为了跟进这些观察结果，我们已经表征了ESCO 2在非洲爪蟾卵提取物中的稳定性，这是一种无细胞系统，在体外重现了凝聚力的建立。我们发现ESCO 2在该系统中的DNA复制过程中是稳定的。事实上，通过诱导DNA损伤信号传导或增加经历DNA复制的细胞核的数量来进一步挑战该系统对ESCO 2的稳定性没有显著影响。在转基因体细胞系中，使用流式细胞术和活细胞成像，我们也没有看到GFP-ESCO 2在细胞周期的S期降解的证据。我们的结论是，ESCO 2是稳定的DNA复制过程中，在胚胎和体细胞。在线版本包含补充材料，可通过10.1007/s10577-023-09711-1获得。
Cohesion between sister chromatids by the cohesin protein complex ensures accurate chromosome segregation and enables recombinational DNA repair. Sister chromatid cohesion is promoted by acetylation of the SMC3 subunit of cohesin by the ESCO2 acetyltransferase, inhibiting cohesin release from chromatin. The interaction of ESCO2 with the DNA replication machinery, in part through PCNA-interacting protein (PIP) motifs in ESCO2, is required for full cohesion establishment. Recent reports have suggested that Cul4-dependent degradation regulates the level of ESCO2 protein following replication. To follow up on these observations, we have characterized ESCO2 stability in Xenopus egg extracts, a cell-free system that recapitulates cohesion establishment in vitro. We found that ESCO2 was stable during DNA replication in this system. Indeed, further challenging the system by inducing DNA damage signaling or increasing the number of nuclei undergoing DNA replication had no significant impact on the stability of ESCO2. In transgenic somatic cell lines, we also did not see evidence of GFP-ESCO2 degradation during S phase of the cell cycle using both flow cytometry and live-cell imaging. We conclude that ESCO2 is stable during DNA replication in both embryonic and somatic cells. The online version contains supplementary material available at 10.1007/s10577-023-09711-1.
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