Systematic reduction of cohesin differentially affects chromosome segregation, condensation, and DNA repair.
Systematic reduction of cohesin differentially affects chromosome segregation, condensation, and DNA repair.
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DOI：
10.1016/j.cub.2010.04.018
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发表时间：
2010-05-25
期刊：
影响因子：
9.2
通讯作者：
Koshland, Douglas
中科院分区：
文献类型：
--
作者：
Heidinger-Pauli, Jill M.;Mert, Ozlem;Davenport, Carol;Guacci, Vincent;Koshland, Douglas
Cohesin’s complex distribution on chromosomes and its implication in numerous cellular processes makes it an excellent paradigm for studying the relationship between the in vivo concentration of a protein and its in vivo function. Here, we report a method to generate systematic quantized reductions (QR) in the in vivo concentration of any yeast protein. Using QR, we generate strains with 13% and 30% of wild-type levels of the limiting subunit of cohesin, Mcd1p/Scc1p/Rad21p. Reducing cohesin levels reveals a preferential binding of cohesin to pericentric regions over cohesin-associated regions (CAR) on chromosome arms. Chromosome condensation, repetitive DNA stability, and DNA repair are compromised by decreasing cohesin levels to 30% of wild-type levels. In contrast, sister chromatid cohesion and chromosome segregation are unaffected even when cohesin levels are reduced to 13% of wild-type levels. The requirement for different in vivo cohesin concentrations to achieve distinct cohesin functions provides an explanation for how cohesin mutations can specifically lead to adult disorders such as Cornelia de Lange Syndrome and Roberts Syndrome without compromising the cell divisions needed for development and maturation. Our successful application of QR to cohesin suggests that QR is a powerful tool to study other proteins/pathways with multiple functions.
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DOI：
10.1083/jcb.200605074
发表时间：
2006-08-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ding DQ;Sakurai N;Katou Y;Itoh T;Shirahige K;Haraguchi T;Hiraoka Y
通讯作者：
Hiraoka Y
影响因子：
16
作者：
Huang, J;Hsu, JM;Laurent, BC
通讯作者：
Laurent, BC
影响因子：
5.3
作者：
Baetz, KK;Krogan, NJ;Hieter, P
通讯作者：
Hieter, P
影响因子：
9.8
作者：
Weber, SA;Gerton, JL;Megee, PC
通讯作者：
Megee, PC
影响因子：
16
作者：
Megee, PC;Mistrot, C;Koshland, D
通讯作者：
Koshland, D