October 25, 2002
Chromosome Twin Sisters Used To Repair DNA Damage

Each cell gets on average 20,000 mutations per day on its chromosomes. There are a number of repair mechanisms for dealing with this damage. These Israeli scientists have demonstrated a long hypothesized repair mechanism. Since chromosomes come in pairs it is possible for a cell to repair one chromosome by copying the equivalent section of the other member of its pair:

The other last-resort repair system was hypothesized by scientists in the 1960s yet was never proved until the current study. This system, which relies on the help of “sister chromosomes,” enables the cell to repair genetic damage without the risk of creating mutations. (During the process of cell division, each chromosome - the structure in the nucleus that contains DNA - gives rise to two identical “sister” chromosomes. These move on to the two separate cells created from the dividing cell.)

According to this theory, if one of the sister chromosomes is damaged, the other can serve as a back-up system of sorts. The damaged genetic information can be restored precisely using the corresponding DNA segment from the other, identical chromosome. That segment detaches itself from the intact “sister” chromosome and moves over to the defective chromosome, helping to repair the damage. The gap created in the donor chromosome is refilled by using the segment from its remaining intact DNA strand (DNA consists of two matching strands) as a template. Both chromosomes end up with a complete, undamaged genetic segment.

In the new study, Prof. Zvi Livneh, head of the Biological Chemistry Department at the Weizmann Institute of Science, has for the first time observed this repair mechanism in action. Furthermore, Livneh and his team, which consisted of graduate students Ala Berdichevsky and Lior Izhar, also showed that the repair mechanism based on a genetic “donation” from the sister chromosome is unusually common: it is responsible for 85% of last-resort repairs – those performed by alternative repair systems when the major, “all-or-nothing” repair mechanism fails. The second last-resort system – the relatively inaccurate repair mechanism that allows the creation of mutations – is responsible only for some 15% of repairs.

Keep in mind the limitations of this repair technique. First of all, it doesn't work on males for X chromosomes since males have only one X chromosome. Also, the copied section may be different than what it replaces because there is considerable genetic variation between the chromosomes people get from each parent. Its possible that by doing the copy a harmful mutation that was silent on one chromososome could get copied to the other so that then two copies of the harmful mutation would exist in the same cell. Still, the vast bulk of the time when this repair mechanism is used the result is beneficial.

It is conceivable that some day this repair mechanism could be hijacked by gene therapy delivery mechanisms to replace sections of a chromosome with new and improved genetic code. The gene therapy could cause a piece of chromosome to be recognized as damaged, a mini-chromosome could be introduced that looked like the matching pair member so that the replacement DNA would be copied from the new mini-chromosome. So this latest research result may eventually be useful for genetically-based treatments.

Share |      Randall Parker, 2002 October 25 01:10 PM  Biotech Manipulations


Comments
JOSH MCNAUGHTON said at January 5, 2004 12:20 PM:

how the did the twin sisters get their name?
how was it givin to them

Maria said at June 22, 2005 10:44 AM:

I like this hypothesis but it is very difficult to check it!

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