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Functional cooperation between FACT and MCM is coordinated with cell cycle and differential complex formation

Functional cooperation between FACT and the MCM helicase complex constitutes an integral step during DNA replication initiation. However, mode of regulation that underlies the proper functional interaction of FACT and MCM is poorly understood. Methods & Results: Here we present evidence indicating that such interaction is coordinated with cell cycle progression and differential complex formation. We first demonstrate the existence of two distinct FACT-MCM subassemblies, FACT-MCM2/4/6/7 and FACT-MCM2/3/4/5. Both complexes possess DNA unwinding. | Tan et al. Journal of Biomedical Science 2010 17 11 http www.jbiomedsci.eom content 17 1 11 I NSC The cost of publication in Journal of Biomedical Science is bourne by the National Science Council Taiwan. JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Functional cooperation between FACT and MCM is coordinated with cell cycle and differential complex formation Bertrand Chin-Ming Tan 21 Hsuan Liut1 Chih-Li Lin 1 and Sheng-Chung Lee 2 3 Abstract Background Functional cooperation between FACT and the MCM helicase complex constitutes an integral step during DNA replication initiation. However mode of regulation that underlies the proper functional interaction of FACT and MCM is poorly understood. Methods Results Here we present evidence indicating that such interaction is coordinated with cell cycle progression and differential complex formation. We first demonstrate the existence of two distinct FACT-MCM subassemblies FACT-MCM2 4 6 7 and FACT-MCM2 3 4 5. Both complexes possess DNA unwinding activity and are subject to cell cycle-dependent enzymatic regulation. Interestingly analysis of functional attributes further suggests that they act at distinct and possibly sequential steps during origin establishment and replication initiation. Moreover we show that the phosphorylation profile of the FACT-associated MCM4 undergoes a cell cycle-dependent change which is directly correlated with the catalytic activity of the FACT-MCM helicase complexes. Finally at the quaternary structure level physical interaction between FACT and MCM complexes is generally dependent on persistent cell cycle and further stabilized upon S phase entry. Cessation of mitotic cycle destabilizes the complex formation and likely leads to compromised coordination and activities. Conclusions Together our results correlate FACT-MCM functionally and temporally with S phase and DNA replication. They further demonstrate that enzymatic activities intrinsically important for DNA replication are tightly .