- 作者: Bertrand Chin-Ming Tan, Hsuan Liu, Chih-Li Lin, Sheng-Chung Lee
- 作者服務機構: Department of Life Science, College of Medicine, Chang Gung Univeristy, Taoyuan, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
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 controlled at various levels, thereby ensuring proper
progression of, as well as exit from, the cell cycle and ultimately euploid gene balance. - 中文關鍵字: --
- 英文關鍵字: --