Chl1 DNA helicase and Scc2 function in chromosome condensation through cohesin deposition.
Chl1 DNA helicase and Scc2 function in chromosome condensation through cohesin deposition.
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DOI：
10.1371/journal.pone.0188739
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Skibbens RV
中科院分区：
文献类型：
--
作者：
Shen D;Skibbens RV
Chl 1 DNA解旋酶促进姐妹染色单体的凝聚力，并与凝聚力建立乙酰转移酶Eco 1/Ctf 7和DNA聚合酶持续合成因子PCNA，支持Eco 1/Ctf 7功能。CHL 1突变导致早熟姐妹染色单体分离和细胞非整倍性，缺陷是通过降低染色质结合的粘附素水平而产生的，该粘附素通常将姐妹染色单体拴在一起（transtethering）。Chl 1家族成员（BACH 1/BRIP/FANCJ和DDX 11/ChlR 1）的突变也表现出遗传毒性敏感性，这与Chl 1在有效DNA修复所需的transtethering中的作用一致。Chl 1促进Scc 2向DNA的募集，这是粘附素沉积到DNA上所需的。然而，有有限的证据表明，Scc 2也指导凝聚素沉积到DNA上，从而促进顺式拴系（分子内DNA连接）。在这里，我们测试的能力，Chl 1促进顺式拴系和Chl 1和Scc 2的作用，以促进凝聚素招聘到DNA。结果表明，chl 1突变细胞表现出显着的凝聚缺陷内的rDNA位点和全基因组。重要的是，chl 1突变细胞凝聚缺陷不导致减少染色质结合凝聚素，而是通过减少染色质结合的粘附素。我们测试了scc 2 -4突变细胞，同样没有发现减少凝聚素募集到染色质的证据。与Scc 2在粘附素沉积中的特异性作用一致，scc 2 -4突变细胞凝聚缺陷是不可逆的。因此，我们术语Chl 1的染色质凝聚和姐妹染色单体凝聚力通过基于凝聚素的机制的一种新的调节剂。这些结果揭示了DNA结构和高度保守的粘附素复合物之间令人兴奋的界面。
Chl1 DNA helicase promotes sister chromatid cohesion and associates with both the cohesion establishment acetyltransferase Eco1/Ctf7 and the DNA polymerase processivity factor PCNA that supports Eco1/Ctf7 function. Mutation in CHL1 results in precocious sister chromatid separation and cell aneuploidy, defects that arise through reduced levels of chromatin-bound cohesins which normally tether together sister chromatids (trans tethering). Mutation of Chl1 family members (BACH1/BRIP/FANCJ and DDX11/ChlR1) also exhibit genotoxic sensitivities, consistent with a role for Chl1 in trans tethering which is required for efficient DNA repair. Chl1 promotes the recruitment of Scc2 to DNA which is required for cohesin deposition onto DNA. There is limited evidence, however, that Scc2 also directs the deposition onto DNA of condensins which promote tethering in cis (intramolecular DNA links). Here, we test the ability of Chl1 to promote cis tethering and the role of both Chl1 and Scc2 to promote condensin recruitment to DNA. The results reveal that chl1 mutant cells exhibit significant condensation defects both within the rDNA locus and genome-wide. Importantly, chl1 mutant cell condensation defects do not result from reduced chromatin binding of condensin, but instead through reduced chromatin binding of cohesin. We tested scc2-4 mutant cells and similarly found no evidence of reduced condensin recruitment to chromatin. Consistent with a role for Scc2 specifically in cohesin deposition, scc2-4 mutant cell condensation defects are irreversible. We thus term Chl1 a novel regulator of both chromatin condensation and sister chromatid cohesion through cohesin-based mechanisms. These results reveal an exciting interface between DNA structure and the highly conserved cohesin complex.
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影响因子：
4.8
作者：
Guo, Manhong;Hundseth, Kristian;Wu, Yuliang
通讯作者：
Wu, Yuliang
DOI：
10.1038/nrg3296
发表时间：
2012-11
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1007/s00018-014-1569-4
发表时间：
2014-07
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Bharti SK;Khan I;Banerjee T;Sommers JA;Wu Y;Brosh RM Jr
通讯作者：
Brosh RM Jr
影响因子：
14.9
作者：
Hirota, Y;Lahti, JM
通讯作者：
Lahti, JM
影响因子：
4.8
作者：
Farina, Andrea;Shin, Jae-Ho;Hurwitz, Jerard
通讯作者：
Hurwitz, Jerard