RNA-making apparatus seen to uncoil and recoil DNA

70652986 — Mon, 26 Mar 2007 06:24:08 -0400

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.

Molecule implicated in transcription termination

70652986 — Mon, 26 Mar 2007 05:36:31 -0400

When a protein is made its DNA code must first be rewritten as messenger RNA (mRNA). This process of transcription requires a large enzyme complex, RNA polymerase, to begin at the start of a gene, work its way along copying the DNA into mRNA, and then stop when it gets to the end. Therein lies a problem. Though there are certain DNA sequences that denote the beginning of a gene, there are no signals to mark the end. Why doesn't the RNA polymerase just keep going? For decades scientists have puzzled over this question. Now, in the Nov. 25, 2005 Nature, Harvard Medical School professor of biological chemistry and molecular pharmacology Stephen Buratowski provides an answer. The key lies in a certain ribonuclease enzyme. Called Rat1, the enzyme can start at the head of a growing RNA and chew up the whole chain. Normally, the growing mRNA is spared this fate because its head is protected by a chemical cap. But as RNA polymerase nears the end of a gene, it incorporates a special sequence called a polyadenine (polyA) signal. Once this happens, the growing RNA gets cut, exposing a new uncapped head.

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RNA-making apparatus seen to uncoil and recoil DNA

Molecule implicated in transcription termination