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Replication-associated mutational asymmetry in the human genome
Chun-Long Chen1, Lauranne Duquenne, Benjamin Audit
1Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique (CNRS), Gif-sur-Yvette, France.
Molecular Biology and Evolution
|March 4, 2011
Summary
DNA replication, like transcription, creates strand-specific mutations. This study reveals replication-associated mutational asymmetries in the human genome, impacting DNA composition.
Area of Science:
- Genomics
- Molecular Biology
- Evolutionary Biology
Background:
- Mutations can occur at different rates on DNA strands, leading to transcription-associated compositional skews.
- Replication-associated mutational asymmetries have not been previously established.
Purpose of the Study:
- To investigate and quantify mutational asymmetries associated with DNA replication in the human genome.
- To differentiate replication-associated asymmetries from transcription-associated ones.
Main Methods:
- Analysis of nucleotide substitution matrices around replication initiation zones.
- Identification of replication timing profiles and compositional skew jumps.
- Modeling of replication errors and strand-biased repair.
Main Results:
- Replication initiation zones explain abrupt jumps in compositional skew.
- Mutational asymmetries in intergenic regions change sign around initiation zones, suggesting replication-based mechanisms.
- Separation of replication and transcription-associated asymmetries in transcribed regions.
Conclusions:
- DNA replication contributes significantly to human genome composition through strand-specific mutations.
- Replication-associated asymmetry may arise from polymerase misincorporation and differential DNA mismatch repair efficiency on leading/lagging strands.
- Replication and transcription equally shape compositional skew in the human genome.
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