DNA Repair Requires Teamwork

DNA Repair Requires Teamwork
As if the genetic code itself were not incredible enough,
researchers have been finding systems that repair it. There
are numerous pathways the cell can embark on to fix DNA errors.
Two key players were recently described in more detail in the
journal Science.1
A damaged genetic code is worse than a book with typos.
Broken or mismatched DNA strands can lead to serious diseases
and even death. It is essential that DNA damage be recognized
and repaired quickly. ScienceDaily2 reported results by a team at
Rockefeller University and Harvard Medical School that found
two essential proteins that act like “molecular tailors” that can snip
out an error and sew it back up with the correct molecules. These
proteins, FANC1 and FANCD2, repair inter-strand crosslinks,
“one of the most lethal types of DNA damage.” This
problem “occurs when the two strands of the double
helix are linked together, blocking replication and transcription.”
Each of your cells is likely to get 10 alarm
calls a day for inter-strand crosslinks.
What do the proteins do to fix it? They link together and join
other members of the repair pathway. The scientists found that
FANC1 and FANCD2 are intimately involved in the excision and
insertion steps.
This one repair operation requires 13 protein parts. “If any
one of the 13 proteins in this pathway is damaged, the result is
Fanconi anemia, a blood disorder that leads to bone marrow failure
and leukemia, among other cancers, as well as many physiological
defects,” the article said. The original paper put it, “Our results
show that multiple steps of the essential S-phase ICL repair mechanism
fail when the Fanconi anemia pathway is compromised.”
Neither the paper nor the press release said anything about how
this tightly-integrated system might have evolved.

1. Knipscheer, P., M. Raschle, A. Smogorzewska, M. Enoiu, T.V. Ho, O.D.
Scharer, S.J. Elledge, and J.C. Walter. 2009. The Fanconi Anemia Pathway
Promotes Replication-Dependent DNA Interstrand Cross-Link Repair. Science
326:1698–1701.
2. Rockefeller University (2010, January 3). Two proteins act as molecular
tailors in DNA repair. ScienceDaily. Retrieved January 22, 2010, from
www.sciencedaily.com/releases/2009/12/091231154652.htm