2023-04-19 カロリンスカ研究所(KI)
Smc5/6複合体は、他の既知の真核生物SMC複合体と同様に、より大きなDNAループを押し出し、ループを形成するために2つの複合体を必要とします。研究チームは、この新しく発見されたメカニズムが、この複合体のウイルス遮断、がん予防、胎児の発育に寄与する能力にどのように関係しているかを研究したいと考えています。
<関連情報>
- https://news.ki.se/nature-study-reveals-new-mechanism-for-dna-folding
- https://www.nature.com/articles/s41586-023-05963-3
Smc5/6複合体はDNAのループを押し出すモーターである The Smc5/6 complex is a DNA loop-extruding motor
Biswajit Pradhan,Takaharu Kanno,Miki Umeda Igarashi,Mun Siong Loke,Martin Dieter Baaske,Jan Siu Kei Wong,Kristian Jeppsson,Camilla Björkegren & Eugene Kim
Nature Published:19 April 2023
DOI:https://doi.org/10.1038/s41586-023-05963-3
Abstract
Structural maintenance of chromosomes (SMC) protein complexes are essential for the spatial organization of chromosomes1. Whereas cohesin and condensin organize chromosomes by extrusion of DNA loops, the molecular functions of the third eukaryotic SMC complex, Smc5/6, remain largely unknown2. Using single-molecule imaging, we show that Smc5/6 forms DNA loops by extrusion. Upon ATP hydrolysis, Smc5/6 reels DNA symmetrically into loops at a force-dependent rate of one kilobase pair per second. Smc5/6 extrudes loops in the form of dimers, whereas monomeric Smc5/6 unidirectionally translocates along DNA. We also find that the subunits Nse5 and Nse6 (Nse5/6) act as negative regulators of loop extrusion. Nse5/6 inhibits loop-extrusion initiation by hindering Smc5/6 dimerization but has no influence on ongoing loop extrusion. Our findings reveal functions of Smc5/6 at the molecular level and establish DNA loop extrusion as a conserved mechanism among eukaryotic SMC complexes.
