RNA-making apparatus seen to uncoil and recoil DNA

2 min read

Eukaryotic cells like to keep their DNA under wraps, winding the long strands of nucleic acid around millions of little protein complexes. This bead-on-a-string structure, called chromatin, ensures that the DNA is protected and also helps to condense the long strands of nucleic acid so they more easily are accommodated in the nucleus.

Chromatin also makes life slightly more complex, however, because it must be unwound when specific genes are to be transcribed into RNA for protein synthesis then rewound when the gene is shut off. Though considerable advances have been made unraveling the mysteries of chromatin disassembly, figuring out how the reassembly occurs has been more challenging. But recent work from Harvard Medical School Professors Kevin Struhl, the David Wesley Gaiser professor of biological chemistry and molecular pharmacology, and Stephen Buratowski, professor of biological chemistry and molecular pharmacology, reveals that the process requires the cooperation of the transcription machinery itself. In the Nov. 18, 2005 Cell and the Dec. 22, 2005 Molecular Cell, Buratowski and Struhl, respectively, show that restoration of the chromatin structure depends on the chemical modification of core histones, the proteins that make up the chromatin bead. When acetyl groups are added to histone proteins they lose some affinity for DNA. This is partly why chromatin falls apart in the first place. But what Struhl, Buratowski, and colleagues show is that deacetylation, which helps to restore chromatin, depends on proteins associated with RNA polymerase II, the enzyme that transcribes DNA into RNA.

The work suggests that just as the transcription machinery promotes unwinding of chromatin as it travels along the DNA making RNA, it also helps to protect the DNA by repackaging the unraveled chromatin it leaves in its wake. The findings lend support to the theory, proposed independently by Struhl and HMS professor of genetics Fred Winston, that restoring the chromatin structure is essential, particularly because it eliminates a potentially disastrous scenario the initiation of DNA transcription in the wrong place, which could lead to cell death.