Stressed cells trigger DNA repair missteps and speed evolution

[Guest guest]

Stressed cells trigger DNA repair missteps and speed evolution

http://www.medicalnewstoday.com/medicalnews.php?newsid=30680

16 Sep 2005

When Dr Rosenberg, professor of molecular and human genetics at

Baylor College of Medicine, first published her finding that the

mutation rate increased in bacteria stressed by starvation, sometimes

resulting in a rare change that benefited the bacteria, it was

controversial.

In a report in the current issue of the journal Molecular Cell, she

and her colleagues describe not only how it happens but also show

that this only occurs at a special time and place in the stressed

cells.

It all begins with the way that the cell repairs breaks in the double

strands of DNA that are its genetic blue print. Usually, when this

happens, special protein machinery in the cell copies the missing DNA

from another chromosome and rejoins the broken ends around the newly

synthesized genetic material.

" It fixes the hole in the DNA by copying similar information, " said

Rosenberg. However, when the process goes wrong, the repair process

introduces errors into the DNA.

When graduate student G. Ponder set up a system so that she

could control where the break in DNA occurred, she found that errors

occurred right next to the break in the stressed cells, and that the

rate of errors was 6,000 fold higher than in cells whose DNA was not

broken. " It's really about local repair, " said Rosenberg. Not only

that, but subsequent experiments proved that this mechanism of

increased mutation at sites of DNA repair occurs only in the cells

under stress. " Even if you get a break in a cell, it won't process it

in a mutagenic way, " said Rosenberg. " The cell repairs it, but does

not make mutations unless the cell is stressed. "

The findings support the notion that the increased mutation rate may

give the cells a selective advantage, she said. Faced with

starvation, most cells do not increase their mutation rate. Then if

food becomes available again, they do well.

Among the small percentage that do increase mutations, most of the

errors are neutral, not affecting cells at all. Many are deleterious,

resulting in cell death. But a small percentage is advantageous,

allowing the cells to survive in an adverse environment.

The fact that the changes in the rate of mutation occur only in a

certain physical space at a certain time gives the cells advantage

because it reduces the risk to the whole colony. DNA breaks occur

only rarely in each individual cell. If the mutations are restricted

in time and space, it reduces the risk that the mistakes in repair

will affect some other gene. It can also enhance the likelihood of

two mutations occurring in the same gene or neighboring genes.

" This can speed evolution of complex protein machines. " Rosenberg

said.

C. Fonville also contributed to this research, which was

supported by grants from the U.S. Department of Defense Breast Cancer

Research Program and the National Institutes of Health.