E3 SUMO-protein ligase NSE2

Definition:

E3 SUMO-protein ligase component of the SMC5-SMC6 complex, a complex involved in DNA double-strand break repair by homologous recombination. Is not be required for the stability of the complex. The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks. The complex is required for telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines and mediates sumoylation of shelterin complex (telosome) components which is proposed to lead to shelterin complex disassembly in ALT-associated PML bodies (APBs). Acts as an E3 ligase mediating SUMO attachment to various proteins such as SMC6L1 and TSNAX, the shelterin complex subunits TERF1, TERF2, TINF2 and TERF2IP, RAD51AP1, and maybe the cohesin components RAD21 and STAG2. Required for recruitment of telomeres to PML nuclear bodies. SUMO protein-ligase activity is required for the prevention of DNA damage-induced apoptosis by facilitating DNA repair, and for formation of APBs in ALT cell lines. Required for sister chromatid cohesion during prometaphase and mitotic progression.

References:

[1]. Patrick Ryan Potts, et al. Human MMS21/NSE2 is a SUMO ligase required for DNA repair. Mol Cell Biol. 2005 Aug;25(16):7021-32. [Content Brief]

[2]. Jonathan Barroso-González, et al. RAD51AP1 Is an Essential Mediator of Alternative Lengthening of Telomeres. Mol Cell. 2019 Oct 3;76(1):11-26.e7. [Content Brief]

[3]. Susanne Behlke-Steinert, et al. SMC5 and MMS21 are required for chromosome cohesion and mitotic progression. Cell Cycle. 2009 Jul 15;8(14):2211-8. [Content Brief]

[4]. Patrick Ryan Potts, et al. The SMC5/6 complex maintains telomere length in ALT cancer cells through SUMOylation of telomere-binding proteins. Nat Struct Mol Biol. 2007 Jul;14(7):581-90. [Content Brief]

[5]. Patrick Ryan Potts, et al. Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks. EMBO J. 2006 Jul 26;25(14):3377-88. [Content Brief]

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