Change search
Link to record
Permanent link

Direct link
BETA
Akkuratov, Evgeny E.
Publications (2 of 2) Show all publications
Seplyarskiy, V. B., Akkuratov, E. E., Akkuratova, N., Andrianova, M. A., Nikolaev, S. I., Bazykin, G. A., . . . Sunyaev, S. R. (2019). Error-prone bypass of DNA lesions during lagging-strand replication is a common source of germline and cancer mutations. Nature Genetics, 51(1), 36-+
Open this publication in new window or tab >>Error-prone bypass of DNA lesions during lagging-strand replication is a common source of germline and cancer mutations
Show others...
2019 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 1, p. 36-+Article in journal (Refereed) Published
Abstract [en]

Studies in experimental systems have identified a multitude of mutational mechanisms including DNA replication infidelity and DNA damage followed by inefficient repair or replicative bypass. However, the relative contributions of these mechanisms to human germline mutation remain unknown. Here, we show that error-prone damage bypass on the lagging strand plays a major role in human mutagenesis. Transcription-coupled DNA repair removes lesions on the transcribed strand; lesions on the non-transcribed strand are preferentially converted into mutations. In human polymorphism we detect a striking similarity between mutation types predominant on the non-transcribed strand and on the strand lagging during replication. Moreover, damage-induced mutations in cancers accumulate asymmetrically with respect to the direction of replication, suggesting that DNA lesions are resolved asymmetrically. We experimentally demonstrate that replication delay greatly attenuates the mutagenic effect of ultraviolet irradiation, confirming that replication converts DNA damage into mutations. We estimate that at least 10% of human mutations arise due to DNA damage.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Biological Sciences
Identifiers
urn:nbn:se:kth:diva-240991 (URN)10.1038/s41588-018-0285-7 (DOI)000454108800011 ()30510240 (PubMedID)2-s2.0-85058128183 (Scopus ID)
Note

QC 20190110

Available from: 2019-01-10 Created: 2019-01-10 Last updated: 2019-01-15Bibliographically approved
Akkuratov, E. E., Gelfand, M. S. & Khrameeva, E. E. (2018). Neanderthal and Denisovan ancestry in Papuans: A functional study. Paper presented at 8th International Moscow Conference on Computational Molecular Biology (MCCMB), JUL 27-30, 2017, Lomonosov Moscow State Univ, Moscow, RUSSIA. Journal of Bioinformatics and Computational Biology, 16(2), Article ID 1840011.
Open this publication in new window or tab >>Neanderthal and Denisovan ancestry in Papuans: A functional study
2018 (English)In: Journal of Bioinformatics and Computational Biology, ISSN 0219-7200, E-ISSN 1757-6334, Vol. 16, no 2, article id 1840011Article in journal (Refereed) Published
Abstract [en]

Sequencing of complete nuclear genomes of Neanderthal and Denisovan stimulated studies about their relationship with modern humans demonstrating, in particular, that DNA alleles from both Neanderthal and Denisovan genomes are present in genomes of modern humans. The Papuan genome is a unique object because it contains both Neanderthal and Denisovan alleles. Here, we have shown that the Papuan genomes contain different gene functional groups inherited from each of the ancient people. The Papuan genomes demonstrate a relative prevalence of Neanderthal alleles in genes responsible for the regulation of transcription and neurogenesis. The enrichment of specific functional groups with Denisovan alleles is less pronounced; these groups are responsible for bone and tissue remodeling. This analysis shows that introgression of alleles from Neanderthals and Denisovans to Papuans occurred independently and retention of these alleles may carry specific adaptive advantages.

Place, publisher, year, edition, pages
Imperial College Press, 2018
Keywords
Neanderthal, Denisovan, Papuan, Yoruba, D-statistic, GSEA, transcription factor, neurogenesis
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-240147 (URN)10.1142/S0219720018400115 (DOI)000431797900006 ()29739306 (PubMedID)2-s2.0-85046850025 (Scopus ID)
Conference
8th International Moscow Conference on Computational Molecular Biology (MCCMB), JUL 27-30, 2017, Lomonosov Moscow State Univ, Moscow, RUSSIA
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20181214

Available from: 2018-12-14 Created: 2018-12-14 Last updated: 2018-12-14Bibliographically approved
Organisations

Search in DiVA

Show all publications