Radiation & Cancer Protection - Some answers are found in yeast genes

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NIEHS Press Release - What protects us from radiation? Some answers are

found in more than 100 yeast genes - November 18, 2001Tuesday, April

02, 2002 9:25 AM

Radiation Protection - Some answers are found

in yeast genes

 

 

- http://www.niehs.nih.gov/oc/news/resnat.htm -

 

 

EMBARGOED BY JOURNAL NIEHS

PR #01-25NIEHS CONTACT: Bill Grigg

(301) 402-3378

grigg

Lou Rozier (919) 541-1993

 

 

What protects us from radiation? Some answers are found in more than 100

yeast genes

A novel search of 3,760 " nonessential " yeast genes has revealed 107 new

genes that may determine how we resist, or are hurt by, radiation -- and

whether we succumb to, or survive, cancer.

More than tripling the number of mutant genes known to influence radiation

damage, the work was carried out at the National Institute of Environmental

Health Sciences and reported today in the journal Nature Genetics.

Previously, fewer than 30 such genes were known.

 

" Most of the newly characterized mutant genes not only protect against gamma

radiation but provide resistance to other damaging agents, such as

ultraviolet light and the commonly used anti-cancer drugs bleomycin and

camptothecin, " the two senior authors Michael A. Resnick, Ph.D and Craig B.

Bennett, Ph.D., said in a joint statement.

 

" So we anticipate, " their statement continued, " that these findings will

lead not only to new human genes that determine resistance to genetic

damage – but to genes that drug manufacturers can target to make more

effective anti-cancer drugs. "

Like many other recent advances in genetic understanding, today's work was

done using common bakers yeast, called Saccharomyces cerevisiae, the living

substance that makes bread dough rise. This yeast has been a model system

for much molecular genetic research for more than three decades because its

basic cellular mechanisms also exist in mammals. The

 

Resnick laboratory, where the work was performed, pioneered the use of yeast

over 25 years ago in genetic and molecular studies to understand how DNA

double-strand breaks, the major source of radiation-induced genetic damage

and change, are produced and repaired by cells.

 

So many human and mammalian disease genes, as well as genes associated with

the repair of ionizing radiation damage, have subsequently been first

characterized in yeast that Dr. Resnick co-authored an only slightly

tongue-in-cheek scientific report last year in Mutation Research called

" Yeast as honorary mammal. "

 

Sixty-nine of the 107 newly discovered yeast genes affecting responses to

radiation are similar to genes in human. Seventeen of the 69 are similar to

known human genes implicated in cancer.

 

" Our discovery, " Dr. Bennett said, " demonstrates how really important many

of these genes that are ‘non-essential' may be, especially in regard to our

susceptibility to the environment – radiation, cigarette smoke, solvents and

other chemicals, drugs and even certain foods. " Non-essential genes are

those which an organism can literally live without – that is, the organism

or body can still grow if the gene is damaged or even deleted. Some can

become essential when an environmental stress like radiation comes along.

 

The new study was made possible when a consortium, the Yeast Genome Deletion

Project, created sets of yeast strains with a different non-essential gene

deleted from each. To make this huge amount of genetic material rapidly

available to the research community, the strains were distributed by a

private company. The NIEHS laboratory irradiated one sample of each strain

and a second set was kept as a control. When an irradiated mutant strain

failed to thrive and grow, compared to the non-irradiated one, the deleted

gene was considered to affect how the organism resisted radiation.

 

" The difference between our study and earlier studies was that we used

diploid cells, " Dr. Bennett said. " Human cells, except for sperm and

unfertilized ova, are diploid – meaning each cell has two sets of every gene

on two sets of chromosomes, one from the mother and one from the father.

Yeast cells, however, vary. They can be either haploid – having a single set

of genes – or diploid. "

 

" We reasoned that organisms with two copies of chromosomes, like humans,

might respond differently to radiation, " Dr. Resnick said, " so we used

diploid yeast – and, indeed, found many more genes influencing radiation

responses. " This approach may explain why several new classes of genes were

found that deal with environmental insults.

 

Collaborating with Drs. Resnick and Bennett at the NIEHS laboratory were

Kevin Lewis, Ph.D., now at Southwest Texas University, visiting researchers

Gopalakrishnan Karthikeyan, Ph.D.,from India, Kirill S. Lobachev, Ph.D.,

from Russia, Yong H. Jin, Ph.D., from Korea, along with biologists Joan F.

Sterling, and Joyce R. Snipe.

 

The 107 newly identified radiation-related genes, along with some 23 that

were previously identified (and re-identified by the current method) bring

the total to 130. These were revealed from the study of just two-thirds of

the non-essential genes. The number of radiation-protective genes will

likely grow to 170 or so, the researchers speculated, when the remaining

1,200 non-essential genes are examined by Dr. Bennett, now of the Duke

University Medical Center in Durham, N.C., Dr. Resnick and their colleagues.

 

" We are in a very exciting transition to 'functional genomics,' " Dr. Resnick

said. " Other new technologies can show whether a substance or environmental

factor turns an individual gene 'on' or 'off,' and now we can begin to tell

whether that switch means something important. The work in yeast should help

illuminate what the gene does within the human body. "

# # # #

Dr. Resnick may be reached at (919) 541-4480.

Dr. Bennett is at (919) 681-2902.

 

 

The URL for this press release is:

http://www.niehs.nih.gov/oc/news/resnat.htm

 

 

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