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Albany 2013: Book of Abstracts

category image Albany 2013
Conversation 18
June 11-15 2013
©Adenine Press (2012)

Mini-chromosome Maintenance Complexes Form A Filament To Remodel DNA Structure and Topology

Deregulation of mini-chromosome maintenance (MCM) proteins is associated with genomic instability and cellular abnormality. MCM complexes are recruited to replication origins for S phase genome duplication. Paradoxically, MCM proteins are expressed in large excess of the number of origins and are associated with unreplicated chromatin regions away from the origins during G1 and S phases. We report an unusually wide left-handed filament structure for an archaeal MCM, as determined by X-ray and electron microscopy. The crystal structure reveals that an α-helix bundle formed between two neighboring subunits plays a critical role in filament formation which we show through mutation and electron microscopy. The filament interior has a remarkably strong electro-positive surface spiraling along the inner filament channel which we establish as the binding site for double stranded DNA. We find that MCM filament binding to DNA causes dramatic topological changes which negatively supercoil circular DNA through inducing loosening of the double helix. This newly identified biochemical activity of MCM may imply a wider functional role for MCM in DNA metabolism beyond helicase function, for the non-origin bound MCMs. Finally, using yeast genetics, we show that the inter-subunit interactions important for MCM filament formation play a role for cell growth and survival.

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Ian M Slaymaker1
Yang Fu1
Daniel B. Toso3
Nimna Ranatunga1
Aaron Brewster3
Susan L Forsburg1
Z. Hong Zhou3
Xiaojiang S. Chen1

1University of Southern California, Los Angeles, CA 90089, USA
2University of California, Los Angeles, Los Angeles, CA 90095, USA
3University of California Berkeley, CA 94720-3220, USA

Ph: (213) 740-2409
Fx: (213) 740-2437
xiaojiang.chen@usc.edu