Loop extrusion

It is a dynamic process in which structural maintenance of chromosomes (SMC) protein complexes progressively grow loops of DNA or chromatin.

Cohesin mediates chromatin loop formation and stabilization, particularly during interphase in vertebrates, where it facilitates transcriptional regulation by promoting distal enhancer-promoter interactions.

Unlike cohesin and condensin, SMC5/6 is a loop extruding factor which primarily functions in maintaining genome integrity during DNA damage repair and resolving replication stress.

Cycles of ATP binding and hydrolysis mediate conformational changes in the ring structure, driving DNA translocation and stepwise loop extrusion.

[10][11] The dynamic nature of loop extrusion is tightly controlled by accessory factors and post-translational modifications, especially in the case of cohesin.

In vertebrates, NIPBL (and orthologs like Mau2 in yeast or SCC2 and SCC4) is crucial for loading SMC complexes onto DNA, initiating and maintaining active extrusion.

Similarly, SUMOylation, mediated by the NSE2 subunit of the SMC5/6 complex, enhances the recruitment of SMC5/6 to sites of DNA damage, supporting its role in genomic stability.

[26] The first direct evidence of loop extrusion came from in vitro imaging studies on fluorescently labeled DNA with condensin[27] or cohesin.

[4] Loop extrusion has been found across the tree of life with suggested roles in immune response, DNA repair, enhancer-promoter interactions, and mitosis.