Dartmouth researchers find new protein function

January 09, 2009

Discovery contributes to understanding the intricate mechanics of cell division

HANOVER, NH - A group of Dartmouth researchers has found a new function for one of the proteins involved with chromosome segregation during cell division. Their finding adds to the growing knowledge about the fundamental workings of cells, and contributes to understanding how cell function can go wrong, as it does with cancerous cells.

The researchers studied a protein called NOD, distantly related to the motor proteins that power diverse cellular activities, including intracellular transport, signaling, and cell division. They used X-ray crystallography to determine its structure, and then they used enzyme kinetics to find out how it performed. While this protein is found in fruit flies, the results are helpful in determining how related proteins work in humans.

"This study on NOD provided evidence for a new way a kinesin motor could function," said Jared Cochran, a postdoctoral fellow at Dartmouth and the lead author on the study. "Rather than moving on its own, it hitches a ride on the ends of microtubules which results in a dynamic cross-linking between the arms of chromosomes and the cell's growing spindle of microtubules. If NOD doesn't function properly, then the two cells end up with either both or none of that particular chromosome, which is lethal [to the cell and the organism] in most cases."

With colleagues from Lawrence Berkeley National Laboratory, Stowers Institute for Medical Research in Kansas City, Missouri, and Kansas University Medical Center in Kansas City, Kansas, the Dartmouth group published their study in the Jan. 9, 2009, issue of the journal Cell. Their paper is titled, "ATPase Cycle of the Nonmotile Kinesin NOD Allows Microtubule End Tracking and Drives Chromosome Movement."

"Before this study, it had been shown that kinesin motors either walked along their microtubule tracks or functioned to break microtubules apart," says Jon Kull, the senior author on the paper, associate professor of chemistry at Dartmouth, and a 1988 Dartmouth graduate. "This work describes a novel mode for kinesin function, in which NOD does not walk, but rather alternates between grabbing on to and letting go of the end of the growing filament, thereby tracking the end as it grows. The diversity of function of these proteins is remarkable."

One of the authors on the paper, Natasha Mulko, is a 2007 Dartmouth graduate, and worked on this project as her senior honors thesis in chemistry. Mulko is currently a graduate student in dentistry at Creighton University. "Natasha's work was integral to this study as she worked on obtaining and improving the protein crystals necessary to solve the structure," says Kull, her thesis advisor.

Dartmouth College

---

---

	Chromosome 47 Gene tinkering run amuck. Addition of a new chromosome to the human genome has the potential to cure disease, extend life, and augment both intellectual and muscular capabilities. Ruthless people don’t care about the crippling side effects, like memory loss and the immune system's virulent counterattack, and compete with each other for control of this revolutionary discovery, seeing only the dollar signs associated with its marketing. Killing their opponents and the lawmen standing in their way simply makes good business sense.
	Chromosome 6 (Jack Stapleton/Laurie Montgomery) by Berkley Chromosome 6 is a prophetic thriller that challenges the medical ethics of genetic manipulation and cloning in the jungles of equatorial Africa, where one mistake could bridge the gap between man and ape--and forever change the genetic map of our existence...
	Chromosome Abnormalities and Genetic Counseling (Oxford Monographs on Medical Genetics) by R.J.M Gardner (Author), Grant R Sutherland (Author), Lisa G. Shaffer (Author) Chromosome abnormalities have been known for over 50 years, though the methods of analysis have become increasing more sophisticated and precise. Surprisingly, the questions that parents and families raise in genetic counseling have changed little over that period. Questions like, "Why did an abnormality happen? Why did it cause the problems we see in our child? Would it happen again in a future child? How could we avoid it happening again?" are common concerns for families. This new edition of Chromosome Abnormalities and Genetic Counseling deals with these universal questions, and in the context of the recent developments in molecular cytogenetic analysis, but retaining always the major focus on the needs of the families in which these conditions occur. Thoroughly updated once...
	The Calcutta Chromosome: A Novel of Fevers, Delirium & Discovery by Amitav Ghosh (Author) From Victorian lndia to near-future New York, The Calcutta Chromosome takes readers on a wondrous journey through time as a computer programmer trapped in a mind-numbing job hits upon a curious item that will forever change his life. When Antar discovers the battered I.D. card of a long-lost acquaintance, he is suddenly drawn into a spellbinding adventure across centuries and around the globe, into the strange life of L. Murugan, a man obsessed with the medical history of malaria, and into a magnificently complex world where conspiracy hangs in the air like mosquitoes on a summer night.
	Chromosome 4: a Science Fiction, Science Fiction Thriller A science-fiction action thriller set aboard a luxury spaceship on course from Earth to Moon. Roger and Paula Winston seem to be two happily married space tourists on a romantic trip of a lifetime. However, when they are drawn into what appears to be a random act of violence, Roger and Paula reveal themselves as figures in an elaborate con game to sell pharmaceutical secrets to a dirty government official. In this riveting pulse-pounding story things are never what they seem, and anyone could be in on the con. Think Philip K. Dick blended with Michael Crichton.
	Genes, Chromosomes, and Disease: From Simple Traits, to Complex Traits, to Personalized Medicine (FT Press Science) by Nicholas Wright Gillham (Author) This very readable overview of the rise and transformations of medical genetics and of the eugenic impulses that have been inspired by the emerging understanding of the genetic basis of many diseases and disabilities is based on a popular nonmajors course, "Social Implications of Genetics," that Gillham gave for many years at Duke University. The book is suitable for use as a text in similar overview courses about genes and social issues or genes and disease. It gives a good overview of the developments and status of this field for a wide range of biomedical researchers, physicians, and students, especially those interested in the prospects for the new, genetics-based personalized medicine.
	Chromosome Abnormalities and Genetic Counseling (Oxford Monographs on Medical Genetics) by R. J. McKinlay Gardner (Author), Grant R. Sutherland (Author) Chromosomal abnormalities can cause disability in children, and reproductive difficulty in parents. Many parents and couples seek genetic counseling in order to learn why they, or a relative, may have had a child with a particular collection of medical problems and/or intellectual disability. There may have been a history of multiple miscarriage, or infertility. They may want to know the outlook for a pregnancy, and what the risks might be. These and other questions concerning chromosome abnormalities are addressed in this standard text, which will be of interest to genetic counselors, medical geneticists, pediatricians and obstetricians, infertility specialists, and laboratory cytogeneticists. This third edition has been thorougly updated, and is richly illustrated and fully...
	Chromosome 6 by Robin Cook (Author) A thriller from the author of CONTAGION in which an American forensic pathologists investigation into the murder of a notorious underworld figure, leads him to the jungles of equatorial Africa. First published in 1997.
	Praise of Chromosome "Folly": Confessions of an Untamed Molecular Structure (Leverhulme Lectures) by Antonio Lima-de-Faria (Author) When examined carefully at the molecular level, the chromosome turns out to have created its own private world full of tricks, back door exits and novel solutions. This folly makes it an untamed innovator. Geneticists have been bewildered for decades. What kind of creature was actually the chromosome? Was it plastic, changing by innumerous rearrangements and mutations all the time; or was it a rigid structure which has preserved its basic organisation and functions since the dawn of the cell? It is this conflicting state that seems to be at the base of its folly . Perplexed by this behavior, cell biologists have called it a junkyard and even the ultimate parasite. Moreover, the chromosome has been regarded as a passive cell organelle prone to random mutations and subjected to the mercy of...