A Reversible Association between Smc Coiled Coils Is Regulated by Lysine Acetylation and Is Required for Cohesin Association with the DNA. Molecular Cell, 2016.

By Irina Kulemzina1, Keven Ang2, Xiaodan Zhao3, Jun-Thing Teh2, Vikash Verma4, Sasikala Suranthran2, Alap P. Chavda2, Roland G. Huber2, Birgit Eisenhaber2, Frank Eisenhaber5, Jie Yan6, Dmitri Ivanov7

Molecular Cell. September 2016. 63(6). 1044-1054. doi: 10.1016/j.molcel.2016.08.008.

Abstract

Cohesin is a ring-shaped protein complex that is capable of embracing DNA. Most of the ring circumference is comprised of the anti-parallel intramolecular coiled coils of the Smc1 and Smc3 proteins, which connect globular head and hinge domains. Smc coiled coil arms contain multiple acetylated and ubiquitylated lysines. To investigate the role of these modifications, we substituted lysines for arginines to mimic the unmodified state and uncovered genetic interaction between the Smc arms. Using scanning force microscopy, we show that wild-type Smc arms associate with each other when the complex is not on DNA. Deacetylation of the Smc1/Smc3 dimers promotes arms’ dissociation. Smc arginine mutants display loose packing of the Smc arms and, although they dimerize at the hinges, fail to connect the heads and associate with the DNA. Our findings highlight the importance of a “collapsed ring,” or “rod,” conformation of cohesin for its loading on the chromosomes.

 

1Bioinformatics Institute, A(∗)STAR, Singapore 138671, Singapore; Friedrich Miescher Laboratory of the Max Planck Society, Tuebingen 72076, Germany.
2Bioinformatics Institute, A(∗)STAR, Singapore 138671, Singapore.
3Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
4Friedrich Miescher Laboratory of the Max Planck Society, Tuebingen 72076, Germany.
5Bioinformatics Institute, A(∗)STAR, Singapore 138671, Singapore; School of Computer Engineering, Nanyang Technological University, Singapore 637553, Singapore; Department of Biological Sciences, National University of Singapore, Singapore 117597, Singapore.
6Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore; Department of Physics, National University of Singapore, Singapore 117551, Singapore; Center for Bioimaging Sciences, National University of Singapore, Singapore 117557, Singapore.
7Bioinformatics Institute, A(∗)STAR, Singapore 138671, Singapore; Institute of Molecular and Cell Biology, A(∗)STAR, Singapore 138673, Singapore; Friedrich Miescher Laboratory of the Max Planck Society, Tuebingen 72076, Germany; Department of Physics, National University of Singapore, Singapore 117551, Singapore.