Cell division orchestrated by multiple oscillating proteins, new research finds

Apr 19, 2010

(PhysOrg.com) -- New research takes the study of biological rhythms, like the heart beat, to a new level: the cell cycle. Scientists at Rockefeller University have proposed that the orderly succession of events in cell division is governed by a master oscillator, coordinating with independent oscillators that control individual events. Their model suggests that this orderly orchestration is analogous to how our circadian rhythm syncs with the light-dark cycle in our environment.

Cell division is a crucial but dangerous business. It unfolds in a cycle of many steps, including , spindle formation, mitosis and others, and they must happen in the right order to prevent abnormal cell death and cancer formation. New research from Rockefeller University examines the activity of two proteins at the heart of the control system and finds that the cycle has not just one, but several independent processes that help to maintain order. The work suggests that autonomous oscillating proteins may coordinate the events of the cell cycle through a phenomena called “phase-locking,” similar to how our circadian rhythm syncs to the light-dark cycle of our environment.

“Our research suggests that the modern eukaryotic cell-cycle may start from multiple oscillatory modules,” says Ying Lu, a former graduate fellow in Frederick R. Cross’s Laboratory of Yeast , who led the research. “That modularity may provide a functional robustness to .”

At the center of the cell-cycle control system is a protein called cyclin-dependent-kinase (Cdk); Cdk’s independent oscillating activity can establish the pace and order of cell cycle events. The researchers, led by Lu, reasoned that if Cdk oscillation was the only cycle-setting pacemaker in the cell, blocking it would cause the cell cycle to stall.

In experiments published Thursday in Cell, they tested the hypothesis by watching what happens to another important protein in the cell cycle known as Cdc14, which normally moves away from the nucleolus, activates and begins antagonizing Cdk as the cell exits . Using quantitative time-lapse microscopy, the researchers were able to capture the transient Cdc14 movement and activation process. They then blocked Cdk oscillation and overt cell-cycle progression, and surprisingly found that the periodic Cdc14 activation/inactivation continued just as it would in a normally dividing cell. They also discovered a negative feedback pathway underlying this Cdc14 oscillator, a finding which indicates that the cell cycle may be composed of multiple autonomous pacemakers.

The existence of these pacemakers raises another question, says Lu, who is now a postdoc in Marc Kirschner’s lab at Harvard University. How do oscillators with different intrinsic frequencies coordinate with each other to form a coherent cell cycle progression? The experiments suggest that, although Cdc14 activity oscillated at constant Cdk levels, its frequency was controlled by several different Cdk activities, which indicates that autonomous cell-cycle oscillators may coordinate each other through a phenomena called phase-locking. Such a system, which is analogous to day-night cycles entraining our circadian clocks, would help explain the evolution of the cell cycle, and to ensure its accuracy and reliability.

“We think multiple oscillators, as they exist independently in the cell cycle, could achieve coherence through interactions affecting their frequencies,” Lu says.

Explore further: In the 'slime jungle' height matters

More information: Cell 141: 268-279 (April 16, 2010), Periodic Cyclin-Cdk Activity Entrains an Autonomous Cdc14 Release Oscillator, Ying Lu and Frederick R. Cross

add to favorites email to friend print save as pdf

Related Stories

Study: Sugar helps control cell division

Sep 21, 2005

Johns Hopkins scientists in Baltimore say they've discovered a deceptively simple sugar is really a critical regulator of cells' natural life cycle.

Study supports DNA repair-blocker research in cancer therapy

Aug 17, 2009

Scientists at Dana-Farber Cancer Institute have uncovered the mechanism behind a promising new approach to cancer treatment: damaging cancer cells' DNA with potent drugs while simultaneously preventing the cells from repairing ...

Recommended for you

Cell division speed influences gene architecture

20 hours ago

Speed-reading is a technique used to read quickly. It involves visual searching for clues to meaning and skipping non-essential words and/ or sentences. Similarly to humans, biological systems are sometimes ...

Secret life of cells revealed with new technique

22 hours ago

(Phys.org) —A new technique that allows researchers to conduct experiments more rapidly and accurately is giving insights into the workings of proteins important in heart and muscle diseases.

In the 'slime jungle' height matters

23 hours ago

(Phys.org) —In communities of microbes, akin to 'slime jungles', cells evolve not just to grow faster than their rivals but also to push themselves to the surface of colonies where they gain the best access ...

Queuing theory helps physicist understand protein recycling

Apr 22, 2014

We've all waited in line and most of us have gotten stuck in a check-out line longer than we would like. For Will Mather, assistant professor of physics and an instructor with the College of Science's Integrated Science Curriculum, ...

User comments : 0

More news stories

When things get glassy, molecules go fractal

Colorful church windows, beads on a necklace and many of our favorite plastics share something in common—they all belong to a state of matter known as glasses. School children learn the difference between ...

SK Hynix posts Q1 surge in net profit

South Korea's SK Hynix Inc said Thursday its first-quarter net profit surged nearly 350 percent from the previous year on a spike in sales of PC memory chips.