Columbia University Medical Center

DNA Repair: How Chromosomes Find Each Other

Two budding yeast cells. Red and yellow lines trace the paths of two chromosomes during the homology search stimulated by a double-strand break in one of them.

A study by Columbia researchers Judith Miné-Hattab, PhD, and Rodney Rothstein, PhD, found that after a double-strand break in DNA, the mobility of both the broken segment and other, unbroken, chromosomes is greatly increased. This makes it easier for homologous chromosomes to “find” each other.

Each of our 46 chromosomes is composed of double-stranded DNA. During homologous recombination, sections around a double-strand break are cut away, and the ends of the broken DNA molecule invade the homologous—identical or similar—DNA molecule on an unbroken chromosome, to copy the missing information. The search for the homologue is extremely efficient, considering how densely packed DNA is in the cell nucleus.

Using baker’s yeast, the researchers found that prior to damage, homologues occupying separate regions of the nucleus explore about 3 percent of the nuclear volume. After damage, the mobility of both cut and uncut chromosomes increases dramatically; the cut chromosomes explore about 30 percent of the nuclear volume, and the uncut ones about 12 percent.

Since increased DNA mobility can lead to genomic instability and susceptibility to cancer, investigating the mechanism of chromosome dynamics is an important first step in understanding how cells maintain genome integrity.

“Increased chromosome mobility facilitates homology search during recombination” was published online April 8, 2012, in Nature Cell Biology.

 

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