Model and modelers provide an insight into pairing of homologous DNA duplexes
Saturday, 2021/10/02 | 07:04:00
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David E. A. Catcheside; PNAS September 28, 2021 118 (39) e2114127118
Figure: Predicted direct pairing of two 48-bp double helices as the basis for DNA homology recognition. Four–base pair stacked quadruplexes are spaced at intervals of 22 bp with 2.5 helical turns of a right-handed plectonemic coil. The orthogonal views are of the average conformation in a 1-ns all-atom molecular dynamics run in water and potassium ions. Bonding of base pairs in a quadruplex formed of two guanine cytosine base pairs is shown for one quartet (not to scale). An animation of this structure is available (16). Adapted with permission from ref. 4.
How homologous DNA duplexes in chromosomes are checked for correct alignment prior to exchange of genetic information during meiosis in Eukaryotes is a longstanding puzzle, a gap in our knowledge of the molecular processes essential for evolution in the more complex cellular organisms that include fungi, plants, and primates. A mechanism to check correct alignment of homologous DNA duplexes prior to committing to irreversible recombination is essential to limit the usually disastrous consequences of scrambling DNA sequences at random. Early sets of hypotheses for this check involved strand breaks in one duplex and transfer of a strand by RecA proteins to form Watson–Crick base pairing in an intact homologous duplex. These models were attractive as when strand invasion found a homologous sequence, a precursor of a complete exchange event was established. A degree of imperfection in base pairing could lead to a reversal of strand invasion and repair of the initiating duplex. Discovery that recombination is initiated by two strand breaks, rather than more reliably repaired single-strand nicks, complicates but does not eliminate such models. Alternatively, appropriate contortions of DNA that might lead to homology detection between intact DNA duplexes have also been considered.
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