Keeping Chromosomes From Cuddling Up

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Keeping Chromosomes From Cuddling Up

http://www.medicalnewstoday.com/articles/131199.php

If chromosomes snuggle up too closely at the wrong times, the results

can be genetic disaster.

Now researchers have found the molecular machines in fruit flies that

yank chromosomes, the DNA-carrying structures, apart when necessary.

The machines, proteins called condensin II, separate chromosomes by

twisting them into supercoils that kink up and therefore can no

longer touch.

Scientists had known of condensin II but did not know how it

functioned inside cells.

Keeping specific parts of chromosomes from touching can change how

the instructions carried in the DNA are read, said research team

leader Giovanni Bosco of The University of Arizona in Tucson.

" It's like picking up your favorite book and, depending on what chair

you chose to sit in, it turned into a different story -- even though

the printed words in the book never changed, " Bosco, a UA assistant

professor of molecular and cellular biology, wrote in an e-mail.

" This now changes the way we think about genetic information. Taking

a literal reading of it is not what actually happens, " he

wrote. " Instead, context matters. "

The team also found that condensin II plays a key role in making sure

that fruit fly sperm cells each receive the proper number of

chromosomes -- not too many, not too few.

Bosco suspects that condensin II plays the same role in the formation

of human sperm and eggs.

Having too many or too few chromosomes in egg or sperm cells is the

source of several important genetic disorders, including Down

syndrome.

Abnormalities in chromosome number is also the cause of some

miscarriages of early-term fetuses in humans.

The research will be published in two separate papers. " Chromosome

Alignment and Transvection are Antagonized by Condensin II, " by Tom

A. Hartl and Helen F. , UA doctoral students, and Bosco is

scheduled for publication in the Nov. 28 issue of the journal

Science. Bosco is also a member of UA's BIO5 Institute.

Hartl, J. Sweeney and J. Knepler, both at the UA, and

Bosco published their paper, " Condensin II Resolves Chromosomal

Associations to Enable Anaphase I Segregation in Drosophila Male

Meiosis, " in the October 2008 issue of PLoS Genetics. Sweeney and

Knepler were UA undergraduates when they conducted the research.

The National Institutes of Health and the National Science Foundation

funded the research.

Learning how cells control chromosomes and how DNA is transcribed

will lead to better understanding of how an organism's DNA affects

the organism's final form.

Scientists have known for about 50 years that when chromosomes are in

direct contact, the transcription machinery can choose to transcribe

either the gene from the mother or the gene from the father.

Many researchers investigated how the specific genes were brought

close together so that process, known as transvection, could happen.

Bosco wondered, what if the chromosomes stayed stuck together?

To find something that separated chromosomes, he looked for female

fruit flies that were sterile because chromosomes in their eggs had

stuck together.

Once he had those fruit flies, Hartl isolated the gene that kept the

chromosomes from coming apart. He found that the gene coded for

condensin II, indicating that the sterile flies couldn't make

condensin II.

To be able to watch how condensin II affects chromosomes, the

researchers used the salivary glands from normal Drosophila

melanogaster fruit flies. Fruit fly salivary glands are unusual,

because they have many copies of the same chromosome coiled together

like a rope.

Hartl said, " You can actually see chromosomes, because the cells are

so huge and the chromosomes are so huge. "

The team inserted an additional gene into the chromosomes that would

turn the condensin II-producing gene off at 77 F (21 C) and on at 95

F (35 C). The researchers also marked one gene on the chromosomes

with green fluorescent protein, or GFP, to be able to see changes in

the chromosomes' positions.

The scientists then looked at the salivary glands at the two

temperatures to see what happened when condensin II was present and

when it was absent.

Bosco said, " Simply turning the condensin gene on or off, we could

watch the chromosomes move right before our eyes, demonstrating that

condensin was mostly likely the tiny machine that was ripping the

chromosomes apart. "

He said these findings are significant because more and more genetic

tests to sequence people's DNA are becoming available, but the DNA

sequence alone does not completely determine what diseases the person

will have.

Even if it's in the genes, it might not show, he said. " It's what

your cells are doing with your genes that's important. "

To pull the chromosomes apart, condensin II changes its shape.

said the team's next step is figuring out how condensin II proteins

are recruited to the chromosomes and how the condensin II proteins

use the cellular energy packets known as ATP to change shape.