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Biomedical subjects

S Nicolay

Publications and source records attributed to S Nicolay.

4 recordsLinked to original sources

Functional modes of proteins are among the most robust.

It is shown that a small subset of modes which are likely to be involved in protein functional motions of large amplitude can be determined by retaining the most robust normal modes obtained using different protein models. This result should prove helpful in the context of several applications proposed recently, like for solving difficult molecular replacement problems or for fitting atomic structures into low-resolution electron density maps. It may also pave the way for the development of methods allowing us to predict such motions accurately.

Computational Biology↗

From DNA sequence analysis to modeling replication in the human genome.

We explore the large-scale behavior of nucleotide compositional strand asymmetries along human chromosomes. As we observe for 7 of 9 origins of replication experimentally identified so far, the (TA+GC) skew displays rather sharp upward jumps, with a linear decreasing profile in between two successive jumps. We present a model of replication with well positioned replication origins and random terminations that accounts for the observed characteristic serrated skew profiles. We succeed in identifying 287 pairs of putative adjacent replication origins with an origin spacing approximately 1-2 Mbp that are likely to correspond to replication foci observed in interphase nuclei and recognized as stable structures that persist throughout subsequent cell generations.

DNA Replication↗

Low frequency rhythms in human DNA sequences: a key to the organization of gene location and orientation?

We explore large-scale nucleotide compositional fluctuations of the human genome using multiresolution techniques. Analysis of the GC content and of the AT and GC skews reveals the existence of rhythms with two main periods of 110+/-20 kb and 400+/-50 kb that enlighten a remarkable cooperative gene organization. We show that the observed nonlinear oscillations are likely to display all the characteristic features of chaotic strange attractors which suggests a very attractive deterministic picture: gene orientation and location, in relation with the structure and dynamics of chromatin, might be governed by a low-dimensional nonlinear dynamical system.

AT Rich Sequence↗

Transcription-coupled TA and GC strand asymmetries in the human genome.

Analysis of the whole set of human genes reveals that most of them present TA and GC skews, that these biases are correlated to each other and are specific to gene sequences, exhibiting sharp transitions between transcribed and non-transcribed regions. The GC asymmetries cannot be explained solely by a model previously proposed for (G+T) skew based on transitions measured in a small set of human genes. We propose that the GC skew results from additional transcription-coupled mutation process that would include transversions. During evolution, both processes acting on a large majority of genes in germline cells would have produced these transcription-coupled strand asymmetries.

Base Composition↗