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The mutation spectrum in genomic late replication domains shapes mammalian GC content
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. (Andrei Chabes)
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
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2016 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 44, no 9, 4222-4232 p.Article in journal (Refereed) Published
Abstract [en]

Genome sequence compositions and epigenetic organizations are correlated extensively across multiple length scales. Replication dynamics, in particular, is highly correlated with GC content. We combine genome-wide time of replication (ToR) data, topological domains maps and detailed functional epigenetic annotations to study the correlations between replication timing and GC content at multiple scales. We find that the decrease in genomic GC content at large scale late replicating regions can be explained by mutation bias favoring A/T nucleotide, without selection or biased gene conversion. Quantification of the free dNTP pool during the cell cycle is consistent with a mechanism involving replication-coupled mutation spectrum that favors AT nucleotides at late S-phase. We suggest that mammalian GC content composition is shaped by independent forces, globally modulating mutation bias and locally selecting on functional element. Deconvoluting these forces and analyzing them on their native scales is important for proper characterization of complex genomic correlations.

Place, publisher, year, edition, pages
2016. Vol. 44, no 9, 4222-4232 p.
National Category
Cell and Molecular Biology
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URN: urn:nbn:se:umu:diva-119528DOI: 10.1093/nar/gkw268ISI: 000377472100030PubMedID: 27085808OAI: diva2:922001
Available from: 2016-04-21 Created: 2016-04-21 Last updated: 2016-07-14Bibliographically approved

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Marjavaara, LisetteKeszthelyi, AndreaChabes, Andrei
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