Top 7 in Molecular Biology

1. A glowing gene tag
A new, genetically-encoded fluorescent protein created in the lab of Roger Tsien, who shared a Nobel Prize for developing green fluorescent protein (GFP), is poised to revolutionize electron microscopy. Engineered from an Arabidopsis protein, “miniSOG” (for mini Singlet Oxygen Generator) is less than half the size of GFP, binds to a suite of well-characterized proteins, and can faithfully tag a variety of mammalian cells as well as cell in intact rodents and nematodes.

X. Shu, et al., “A genetically encoded tag for correlated light and electron microscopy of intact cells, tissues, and organisms,” PLoS Biology, 9:e1001041, 2011. Free F1000 Evaluation

2. Lighting up RNA
A novel technique for tagging and following RNA processes in live cells promises to illuminate RNA biology the way green fluorescent protein (GFP) did for the study of proteins. The tagging method consists of short RNA sequences that bind to GFP-like fluorophores and produce a wide range of colors. These RNA-fluorophore complexes can then be fused to RNAs in the cell.

J.S. Paige et. al., “RNA mimics of green fluorescent protein,” Science, 333: 642-6, 2011. Free F1000 Evaluation

3. Chromatin, DNA damage response, and cell death

When oncogenes are activated, cells respond by ramping up their DNA damage response (DDR) and going into a state of senescence, most likely as a form of tumor suppression. But as they fill up with heterochromatin, which accumulates with replicative stress, and they switch off the DDR to stay viable. Researchers have found that the ATR (ataxia telangiectasia and Rad3-related) kinase pathway, which mediates heterochromatin production, is key to this switch, a piece of knowledge that could be used to treat some types of cancer.

R. Di Micco, et al., “Interplay between oncogene-induced DNA damage response and heterochromatin in senescence and cancer,” Nat Cell Biol, 13:292-302, 2011. Free F1000 Evaluation

4. Unwinding helicases

How the helicase MCM2-7 unwinds DNA during replication has been a mystery. By determining the structure of MCM2-7, which consists of a six subunit ring, as well as the structure of the proteins it binds to at the origin recognition complex (ORC), researchers found that the helicase is likely locked into chromatin and activated through the binding of two proteins to four of its subunits.

A. Costa et. al., “The structural basis for MCM2-7 helicase activation by GINS and Cdc45,” Nat Struct Mol Biol, 18: 471-7, 2011. Free F1000 Evaluation

5. Ovarian cancer in intimate detail

As part of its goal of detailing genomic changes that occur in 20 cancer types, the Cancer Genome Atlas Research Network performed the first comprehensive genomic analysis of ovarian cancer. A profile of gene and microRNA expression, copy number variation, and sequence and methylation alterations revealed new information about the cellular changes that lead to ovarian tumors, such as extensive copy number changes and the epigenetic silencing of 168 genes.

The Cancer Genome Atlas Research Network, “Integrated genomic analyses of ovarian carcinoma,” Nature, 474: 609-15, 2011. Free F1000 Evaluation

6. Repressing chromatin
Researchers found that an array of nonhistone proteins tightly bound to DNA can cooperate with silencing factors nearby to form tightly bound, silent chromatin. Specifically, the protein-DNA interactions serve to disrupt replication by inhibiting DNA unwinding—suggesting a link between replicative stress and gene silencing.

M. Dubarry et. al., “Tight protein-DNA interactions favor gene silencing,” Genes Dev, 25: 1365-70, 2011. Free F1000 Evaluation

7. How ribosomes unwind

Ribosomes employ two mechanisms for unwinding secondary RNA structures such as “hairpins,” researchers have found. One mechanism involves the destabilization of base pairing, while the other involves mechanically pulling apart the paired strands.

X. Qu et. al., “The ribosome uses two active mechanisms to unwind messenger RNA during translation,” Nature, 475: 118-21, 2011. Free F1000 Evaluation

The F1000 Top 7 is a snapshot of the highest ranked articles from a 30-day period on Faculty of 1000 Molecular Biology, as calculated on August 15, 2011. Faculty Members evaluate and rate the most important papers in their field. To see the latest rankings, search the database, and read daily evaluations, visit

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