High
Scientists make key finding underlying
genetic stability
Biologists at the Laboratory have discovered new insights into how two common proteins found in mammalian cells can cause chromosomes to fuse together -mutations that can destroy cells or give rise to cancer.
The research, by Susan Bailey and Edwin Goodwin of the Biosciences (B) Division, was published recently in the journal Science.
Bailey, Goodwin and their colleagues looked at the role of telomeres in protecting chromosome ends. Chromosomes are made of deoxyribonucleic acid - DNA - and are the carriers of genetic information. Human cells contain 22 pairs of chromosomes plus two gender chromosomes. Telomeres are specialized protective structures at the end of each arm of the X-shaped chromosomes.
Without telomeres, natural chromosome ends appear to the cell like broken DNA ends in need of repair. Mutations in certain genes impair the protective function of telomeres leading to inappropriate "repair," in effect causing chromosomes to fuse together end to end. Chromosome end fusions destabilize the orderly transmission of genetic information to the next generation of cells. The Los Alamos researchers studied telomere dysfunction in order to learn more about how a normal telomere works.
Each chromosome has four telomeres. Mammalian telomeres contain a unique DNA sequence, discovered earlier by Los Alamos' Human Genome Project, as well as specialized proteins that together create a protective cap at the ends of chromosome arms.
Bailey and Goodwin looked at the role of two proteins in telomere function. One protein was known to play a role in telomere function and chromosome end capping. The other protein originally was shown to help repair damaged DNA, but later was shown by Bailey and Goodwin to also help protect natural chromosome ends.
The researchers used human cells provided by Titia DeLange of Rockefeller University that contained artificially induced changes to the first protein and mouse cells with mutations in the second protein. Under normal circumstances, when cells divide they produce exact duplicates, including exact duplicates of the chromosomes they contain. Bailey, Goodwin and their colleagues found that the progeny of cells containing the altered proteins often contained chromosomes that had fused with other chromosomes at one arm. The fused chromosomes had a sausage-like appearance and were easy to distinguish from normal chromosomes. Due to their genetic abnormalities, the damaged daughter cells often were unable to thrive.
The fusing chromosome arms in the dying daughter cells indicated that the malfunction might be associated with telomere replication and indicative that the protein changes induced in the original cells played a role.
But Bailey and Goodwin noticed something else - something extraordinary and unexpected.
Using a Los Alamos-developed technique called chromosome-orientation fluorescence in situ hybridization - CO-FISH -that highlights which half strand of the DNA double helix underwent replication during the cell-division process, the researchers determined that the fusion only occurred on specific arms of the chromosomes. What's more, Bailey and Goodwin noticed that fusion never occurred in a chromosome on two arms on the same-side of the "X"; if more than one fusion occurred in a single chromosome, the fusion always occurred on opposite arms on opposite sides. This indicated to the researchers that not all telomeres in a chromosome are the same, because if they were, the researchers would have expected to see same-side fusion in at least some cases simply based on the laws of chance.
"A lot of research has been done on telomeres in the biological community, and the conventional thought was that all telomeres are created alike," said Goodwin. "Our research shows that this is not the case. There are two different processes for protecting telomeres and they have distinct genetic requirements."
The difference in telomeres apparently lies in the way chromosomes are replicated, Bailey and Goodwin found. When chromosomes duplicate themselves, their DNA double helices separate into two strands and then rebuild their DNA structure on each half strand. Because DNA polymerases - the protein catalysts that make the new DNA strands - proceed in only one direction, the two new telomeres replicated from the original parent telomere are produced by two different mechanisms.
In one case, the telomere's double helix terminates in a blunt end. In the other case, the telomere ends with a minute chemical overhang. This overhang is important because it allows the telomere to loop back on itself - forming a so-called "t-loop" - to complete its end cap. The first process is known as leading-strand DNA synthesis; the second is known as lagging-strand DNA synthesis.
Bailey, Goodwin and their colleagues found that chromosome fusion occurred only at sites on the chromosomes where telomeres had been formed by the leading-strand process.
The research indicates that both altered proteins induced in the cells used for study play a role in capping the ends of telomeres formed by leading-strand DNA synthesis, but are not required to cap telomeres replicated by lagging -- strand synthesis.
Bailey and Goodwin's research is significant because it has shown the existence of two types of telomeres and also gives insight into the roles of two proteins in normal cell function.
All of Bailey's and Goodwin's co-authors of the paper are former Los Alamos researchers, and include: Michael Cornforth, Department of Radiation Oncology, University of Texas Medical Branch; and Akihiro Kurimasa and David Chen, Cell and Molecular Biology Division, Lawrence Berkeley National Laboratory.
--James E. Rickman
Barbecue today at Technical Area 54 raises
funds for United Way September 11th Fund
At noon today Laboratory workers from Facility Waste Operations (FWO) at Technical Area 54 will host a "TA-54 Loves the USA Barbecue" to raise money for the United Way September 11th Fund. Donations will be accepted for the fund in lieu of any charge for lunch. The barbecue is open to all badge holders and there will be food for approximately 250 people.
Workers at TA-54 will be donating the food for the barbecue. Anyone else interested in donating a food item or with questions should contact Lori Mullen or Deba Daymon of Solid Waste Operations (FWO-SWO) at 5-6158.
The barbecue will be on the decks across the street from the FWO-SWO group office at TA-54, which is located off of Pajarito Road. Upon entering TA-54 follow the road paralleling Pajarito Road through the manned guard gate approximately one and one-half miles to a parking lot on the left side of the road. The barbecue is approximately 200 yards from the parking lot.
Laboratory Director John Browne issued an employee memo to Lab workers this week regarding the United Way Campaign. To read the memo, click here. (Adobe Acrobat Reader required).
Laboratory reaches settlement in tissue analysis case
The plaintiffs in a class action lawsuit that involved a long-term tissue analysis program at the Laboratory have reached a settlement agreement with the University of California, which manages the Laboratory for the Department of Energy. The study, which used tissues from autopsies conducted primarily at Los Alamos Medical Center, began in 1959 and ended in 1980.
Details of the $8 million settlement agreement are contained in a document to be filed with the First Judicial District Court in Santa Fe. The court will consider the proposed settlement at a hearing scheduled for Jan. 11, 2002.
The Laboratory acknowledges that because express consent to use the autopsy tissue may not have been obtained from next of kin, the plaintiffs and many of those they represent are aggrieved in this matter.
The Laboratory further acknowledges that while the program was conducted with the best of intentions, and within the legal and ethical standards of the time, if initiated today it would be conducted under current informed consent practices that are more formal and highly detailed.
The Laboratory regrets and understands that even though the program made important contributions to worker and public health knowledge, and benefited the nation by establishing solid long-term radioactive exposure limits, some aspects of the study could be upsetting to those who did not have an opportunity to give their informed consent.
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Los Alamos News Letter This week's Los Alamos News Letter features the Laboratory's 2000 Distinguished Performers. The 2000 Distinguished Performers accomplished many great projects ranging from proton radiography to creating Cerro Grande Fire Web sites, from fissile material storage to a bridge to employement program. Nine individuals, eight small teams and six large teams received awards. The LANL News Letter is distributed to every group office administrator for distribution. Check your mailboxes or get your Los Alamos News Letter at http://www.lanl.gov/worldview/news/LANL/100401.pdf online. It also is available at various bright blue distribution boxes located throughout the Lab. |
Next presentation for expectant parents is Oct. 9
Compensation and Benefits (HR-1) and Occupational Medicine (ESH-2) are sponsoring a presentation for expectant parents from 10 to 11:30 a.m. Tuesday, (Oct. 9), at the Wellness Center at Technical Area 3.
The presentation is in room 106 of the Wellness Center and is open to University of California employees, their spouses and/or partners and subcontract personnel. Registration is required; go to the Virtual Training Center on the Lab's World Wide Web page, select "Workforce Development," and then select "Benefits" to register.
A benefits specialist from HR-1, representatives from ESH-2 and the Diversity Office (DV) will conduct the free presentation.
The benefits specialist will talk about short-term disability. ESH-2 representatives will discuss the Family and Medical Leave Act, maternity and parental-leave and safety issues in the workplace for expectant mothers.
There also will be information about classes and other services offered by the Wellness Center. Information about childcare resources also will be available.
For more information, call HR-1 at 7-1806 or write to benefits@lanl.gov by electronic mail.
To make arrangements for a sign language interpreter, call HR-1 three business days in advance.
--Steve Sandoval
Panel discussion, cooking demonstration
scheduled this month at Lab
Cholesterol Education Month events sponsored by Occupational Medicine
Watching your cholesterol sometimes can be difficult. At two events this month, Laboratory workers can get some help from medical, health and nutrition experts, including a professional chef who will provide tips on heart and cholesterol friendly cooking.
September was national Cholesterol Education Month; the two events on Oct. 11 and 16 were rescheduled because of the incidents last month on the east coast.
The activities are sponsored by the health promotion team in Occupational Medicine (ESH-2) and are free and open to the public.
The first event is at 11:30 a.m. Thursday, Oct. 11 in the Otowi Building side rooms A and B at Technical Area 3. Santa Fe chef Vikki Nulman will give a cooking demonstration with complementary tasting. Nulman has taught healthy cooking courses in the United States, Mexico and Italy. Nulman is the owner and instructor of Chef's at Work. She also is a culinary arts instructor at Santa Fe Community College and president of the American Culinary Federation Chef's of Santa Fe.
From noon to 1 p.m. Oct. 16 in the Materials Science Laboratory Auditorium at TA-3, a panel of health and medical experts will talk about lifestyle changes to help control or improve cholesterol levels. "Take Lifestyle Action to Meet the New Cholesterol Guidelines," includes Los Alamos cardiologist Dr. Anthony Sandoval; Dr. Paul Daly of ESH-2; Marta Gentry Munger, a dietitian; and health and fitness specialist Allen Figg, also of ESH-2.
The panel discussion also will be videotaped for later airing on LABNET Channel 10. The tape also can be checked out to Lab organizations through ESH-2.
"This is an excellent opportunity to learn about the National Institute of Health's new cholesterol guidelines, along with practical tips for putting the recommendations in to action," said Gentry Munger.
Dr. Paul Daly of ESH-2 said the National Institute of Health earlier this year revised its recommendations for optimum HDL and LDL cholesterol levels. He said that 100 is considered the optimum LDL cholesterol level.
A HDL cholesterol level below 40 is considered low. An HDL cholesterol level greater than or equal to 60 is considered desirable and protects against heart disease.
"Although diet may slightly improve a person's HDL level it is regular aerobic exercise that has been shown to significantly raise HDL levels," said Daly.
"Before starting a vigorous exercise program one should consult with their primary care physician," Dr. Daly added.
A total cholesterol level less than 200 is still considered desirable, the NIH said.
Gentry Munger noted that the National Institute of Health's therapeutic lifestyle changes, or TLC program, emphasizes diet and exercise. "Although reducing saturated fat remains the foundation of a heart healthy diet, there are additional options to further enhance cholesterol lowering," she said.
As part of Cholesterol Education Month, a display has been set up in the lobby of the Otowi Building cafeteria on the second floor. The display includes information on how to control and/or lower LDL, the so-called bad cholesterol levels, and increase HDL, or the so-called good cholesterol levels, as well as information on nutrition, stress, screening recommendations, heart disease and other factors that affect cholesterol.
Gentry Munger added that the Wellness Center offers an online healthy eating course. To register and take the course, "Learning to Eat for a Healthy Heart," go to http://drambuie.lanl.gov/~wellness/olrsc/wcol/lehh/lehh_index.htm online.
For more information, contact Gentry Munger at 7-7166 or Jessica Kisiel of ESH-2 at 5-4368.
--Steve Sandoval
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