Cohesin Loading onto Chromatin

Stable Identifier
Homo sapiens
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In mitotic telophase, as chromosomes decondense, cohesin complex associated with PDS5 (PDS5A and PDS5B) and WAPAL (WAPL) proteins is loaded onto chromatin (Shintomi and Hirano, 2009, Kueng et al. 2006, Gandhi et al. 2006, Chan et al. 2012). Cohesin loading is facilitated by the complex of NIPBL (SCC2) and MAU2 (SCC4) proteins, which constitute an evolutionarily conserved cohesin loading complex. MAU2 depletion in HeLa cells results in 2-3-fold reduction in the amount of cohesin in the chromatin fraction (Watrin et al. 2006). NIPBL mutations are the cause of the Cornelia de Lange syndrome, a dominantly inherited disorder characterized by facial malformations, limb defects, and growth and cognitive retardation (Tonkin et al. 2004). Cornelia de Lange syndrome can also be caused by mutations in cohesin subunits SMC1A (Musio et al. 2006, Borck et al. 2007, Deardorff et al. 2007, Pie et al. 2010) and SMC3 (Deardorff et al. 2007).

Literature References
PubMed ID Title Journal Year
16604071 X-linked Cornelia de Lange syndrome owing to SMC1L1 mutations

Musio, A, Selicorni, A, Focarelli, ML, Gervasini, C, Milani, D, Russo, S, Vezzoni, P, Larizza, L

Nat. Genet. 2006
17113138 Wapl controls the dynamic association of cohesin with chromatin

Kueng, S, Hegemann, B, Peters, BH, Lipp, JJ, Schleiffer, A, Mechtler, K, Peters, JM

Cell 2006
19696148 Releasing cohesin from chromosome arms in early mitosis: opposing actions of Wapl-Pds5 and Sgo1

Shintomi, K, Hirano, T

Genes Dev. 2009
16682347 Human Scc4 is required for cohesin binding to chromatin, sister-chromatid cohesion, and mitotic progression

Watrin, E, Schleiffer, A, Tanaka, K, Eisenhaber, F, Nasmyth, K, Peters, JM

Curr. Biol. 2006
20358602 Mutations and variants in the cohesion factor genes NIPBL, SMC1A, and SMC3 in a cohort of 30 unrelated patients with Cornelia de Lange syndrome

Pie, J, Gil-Rodríguez, MC, Ciero, M, López-Viñas, E, Ribate, MP, Arnedo, M, Deardorff, MA, Puisac, B, Legarreta, J, de Karam, JC, Rubio, E, Bueno, I, Baldellou, A, Calvo, MT, Casals, N, Olivares, JL, Losada, A, Hegardt, FG, Krantz, ID, Gomez-Puertas, P, Ramos, FJ

Am. J. Med. Genet. A 2010
17273969 Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation

Deardorff, MA, Kaur, M, Yaeger, D, Rampuria, A, Korolev, S, Pie, J, Gil-Rodríguez, C, Arnedo, M, Loeys, B, Kline, AD, Wilson, M, Lillquist, K, Siu, V, Ramos, FJ, Musio, A, Jackson, LS, Dorsett, D, Krantz, ID

Am. J. Hum. Genet. 2007
17112726 Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase

Gandhi, R, Gillespie, PJ, Hirano, T

Curr. Biol. 2006
17221863 Incidence and clinical features of X-linked Cornelia de Lange syndrome due to SMC1L1 mutations

Borck, G, Zarhrate, M, Bonnefont, JP, Munnich, A, Cormier-Daire, V, Colleaux, L

Hum. Mutat. 2007
22901742 Cohesin's DNA Exit Gate Is Distinct from Its Entrance Gate and Is Regulated by Acetylation

Chan, KL, Roig, MB, Hu, B, Beckouët, F, Metson, J, Nasmyth, K

Cell 2012
15146185 NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome

Tonkin, ET, Wang, TJ, Lisgo, S, Bamshad, MJ, Strachan, T

Nat. Genet. 2004
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