10:44pm Saturday 21 October 2017

Penn Study Finds Cell Division Sign Posts for Chromosomes Along Microtubule Highway

The team found that specific chemical signals on microtubules — which work as an intracellular highway — give directions to chromosomes as to which route to take during cell division. They described their findings this month in Science.

Microtubules are components that give structure to and organize a cell. They are also the main intracellular transport network. Motor proteins move along the microtubules ferrying chromosomes undergoing mitosis (part of cell division) as well as other subcellular organelles. How motor proteins navigate chromosomes along the highway during cell division was unclear, until now. The team discovered marks that label microtubules to direct the way in which a chromosomal motor protein should proceed.

During cell division, chromosomes move on special spindle microtubules to align themselves, so they can split equally between the two resulting daughter cells. The team demonstrated that chromosome motion for this alignment is controlled by a specific post-translational modification of tubulin, the protein building block of microtubule tracks.

The Grishchuk lab showed that transport by a molecular motor protein called CENP-E kinesin is strongly enhanced on certain microtubule tracks. “This biophysical study was complemented by cell biological experiments carried out by the Maiato lab in Portugal, leading to the discovery that CENP-E-kinesin motors failed to take chromosomes to their alignment position if the guiding marks were eliminated,” explains Grishchuk. “This discovery became possible due to our use of high-resolution laser trapping techniques, which enable observing motions and forces at a single molecule level. With these multidisciplinary approaches, we hope to gain understanding of the mechanisms that ensure a high fidelity of chromosome segregation in dividing cells and learn how pathological chromosomal instability can be prevented.”

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Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $4.9 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 years, according to U.S. News & World Report‘s survey of research-oriented medical schools. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $409 million awarded in the 2014 fiscal year.

The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania — recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Penn Wissahickon Hospice; and Pennsylvania Hospital — the nation’s first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2014, Penn Medicine provided $771 million to benefit our community.


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