PubMed Health⌕ Search

PubMed · 12667030

Celebrating complementarity.

Abstract

The 1950s witnessed prodigious growth in our knowledge of the chemical nature of the gene, the mechanisms by which the information inherent in its sequence of nucleotide units was conveyed to the cell's machinery for synthesizing proteins, and the mode of operation of that machinery. Watson and Crick raised the curtain by revealing the structure of DNA, notably the complementary pairing of the nucleotides in its twin chains. Identified with the new field of molecular biology, Crick defined and expanded the field of genetic information coding and led attempts to elucidate principles governing information translation into protein. On a parallel and complementary track, biochemists-notably the group led by Paul Zamecnik-were working out the details of the mechanism of protein synthesis: how and where in the cell amino acids were energized, sequenced, and polymerized. These two approaches to closely related problems, separated by a considerable cultural gap, merged dramatically in 1956. Crick's thinking led him to postulate the existence of adaptors -short chains of RNA nucleotide bases that, when linked to amino acids, might make the latter chemically "recognizable" to an RNA template by complementary pairing of their bases with those of the template. Simultaneously, the Zamecnik group discovered enzymes (amino acyl-tRNA synthetases) capable of energizing amino acids and, thence, attaching them to a hitherto unsuspected cellular RNA (transfer RNA). These RNA molecules, in turn, donated their bound amino acids to elongating protein chains on ribosomes, thus appearing to serve the function of adaptors.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Mahlon B Hoagland. 2003-04-01. Celebrating complementarity.. https://doi.org/10.7326/0003-4819-138-7-200304010-00016

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

VIPR RNA-guided DNA recognition by noncontiguous geometric triplex formation.

Viral interference programmable repeat (VIPR) systems use a noncontiguous code for RNA-guided transcriptional silencing. How the Vipr protein and a VIPR RNA (vrRNA) comprising alternating GGY and NN segments achieve precise DNA targeting is unknown. Here, we present 21 cryo-electron microscopy structures that help explain the mechanism of target engagement. Vipr protomers oligomerize along the vrRNA to form a right-handed helical filament, sequestering each GGY motif and positioning the adjacent NN bases for target base pairing. DNA binding, in which every third nucleotide is skipped, results in a gapped vrRNA-DNA hybrid helix that encircles the nontarget DNA strand to form a geometric triplex. These findings suggest that triplex-mediated target-strand handoff could enable noncontiguous and programmable RNA-guided DNA recognition in VIPR systems.

DNA↗

Caloric restriction modulates genome-wide somatic mutation in mice.

Somatic mutations accumulate throughout life in every cell, and this process constitutes one of the hallmarks of aging-genomic instability. Caloric restriction (CR) has been shown to extend lifespan across diverse species. Using high-fidelity duplex DNA sequencing of bulk liver, bulk kidney, hepatocytes, and cerebellar neurons, we found that CR in mice reduces genome-wide somatic mutation burdens across multiple tissues and cell types. CR reduced both substitution and insertion/deletion burdens, with the magnitude of these effects varying across sample types. CR also decreased the activity of the enigmatic single-base substitution (SBS) mutational process SBS5 that gives rise to most mutations in mammals. Surprisingly, the mutation burden reduction from CR was greatest in transcriptionally inactive regions. This work illuminates links between diet, aging, and genomic integrity and establishes genomic integrity as a modifiable axis of aging.

DNA↗

Maternal DNA repair safeguards genome stability during the oocyte-to-embryo transition.

De novo mutations are a major source of genetic variation and disease risk, yet the developmental timing and mechanisms underlying their origin require further investigation. While germ cells have traditionally been considered the primary source of these mutations, increasing evidence suggests that a substantial fraction arise after fertilization. Here, we investigated the role of maternal DNA repair in shaping mutagenesis during this critical window by using a mouse model with oocyte-specific disruption of the homologous recombination factor RAD51 and a combination of cellular and molecular analyses. Loss of maternal RAD51 led to the accumulation of DNA double-strand breaks in oocytes without impairing their growth, meiotic maturation, or fertilization competence. In contrast, embryos derived from RAD51-deficient oocytes exhibited increased DNA damage and developmental delay during early cleavage stages. Whole-genome sequencing revealed a significant increase in de novo variants in offspring, the majority displaying intermediate allele frequencies consistent with post-zygotic mosaic mutations. These findings confirm that maternal DNA repair safeguards genome stability across the oocyte-to-embryo transition and identify early embryogenesis as a major source of de novo mutations, with implications for reproductive biology and the origins of genetic diseases.

DNA↗