دورية أكاديمية
أعرض في EDS

APOBEC-induced mutations in human cancers are strongly enriched on the lagging DNA strand during replication.

التفاصيل البيبلوغرافية
العنوان: APOBEC-induced mutations in human cancers are strongly enriched on the lagging DNA strand during replication.
المؤلفون: Seplyarskiy VB; Institute of Information Transmission Problems, Russian Academy of Sciences, Moscow, Russia, 127051; Lomonosov Moscow State University, Moscow, Russia, 119991; Pirogov Russian National Research Medical University, Moscow, Russia, 117997;, Soldatov RA; Institute of Information Transmission Problems, Russian Academy of Sciences, Moscow, Russia, 127051; Lomonosov Moscow State University, Moscow, Russia, 119991;, Popadin KY; Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, 1211 Geneva, Switzerland;, Antonarakis SE; Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, 1211 Geneva, Switzerland;, Bazykin GA; Institute of Information Transmission Problems, Russian Academy of Sciences, Moscow, Russia, 127051; Lomonosov Moscow State University, Moscow, Russia, 119991; Pirogov Russian National Research Medical University, Moscow, Russia, 117997;, Nikolaev SI; Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, 1211 Geneva, Switzerland; Service of Genetic Medicine, University Hospitals of Geneva, 1211 Geneva, Switzerland.
المصدر: Genome research [Genome Res] 2016 Feb; Vol. 26 (2), pp. 174-82. Date of Electronic Publication: 2016 Jan 11.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cold Spring Harbor Laboratory Press Country of Publication: United States NLM ID: 9518021 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1549-5469 (Electronic) Linking ISSN: 10889051 NLM ISO Abbreviation: Genome Res Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cold Spring Harbor, N.Y. : Cold Spring Harbor Laboratory Press, c1995-
مواضيع طبية MeSH: Cytidine Deaminase/*physiology , Neoplasms/*genetics, Cytosine/metabolism ; DNA Methylation ; DNA Mutational Analysis ; DNA Replication ; Exome ; Humans ; Mutagenesis ; Mutation ; Mutation Rate
مستخلص: APOBEC3A and APOBEC3B, cytidine deaminases of the APOBEC family, are among the main factors causing mutations in human cancers. APOBEC deaminates cytosines in single-stranded DNA (ssDNA). A fraction of the APOBEC-induced mutations occur as clusters ("kataegis") in single-stranded DNA produced during repair of double-stranded breaks (DSBs). However, the properties of the remaining 87% of nonclustered APOBEC-induced mutations, the source and the genomic distribution of the ssDNA where they occur, are largely unknown. By analyzing genomic and exomic cancer databases, we show that >33% of dispersed APOBEC-induced mutations occur on the lagging strand during DNA replication, thus unraveling the major source of ssDNA targeted by APOBEC in cancer. Although methylated cytosine is generally more mutation-prone than nonmethylated cytosine, we report that methylation reduces the rate of APOBEC-induced mutations by a factor of roughly two. Finally, we show that in cancers with extensive APOBEC-induced mutagenesis, there is almost no increase in mutation rates in late replicating regions (contrary to other cancers). Because late-replicating regions are depleted in exons, this results in a 1.3-fold higher fraction of mutations residing within exons in such cancers. This study provides novel insight into the APOBEC-induced mutagenesis and describes the peculiarity of the mutational processes in cancers with the signature of APOBEC-induced mutations.
(© 2016 Seplyarskiy et al.; Published by Cold Spring Harbor Laboratory Press.)
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المشرفين على المادة: 8J337D1HZY (Cytosine)
EC 3.5.4.5 (Cytidine Deaminase)
تواريخ الأحداث: Date Created: 20160113 Date Completed: 20161019 Latest Revision: 20181113
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC4728370
DOI: 10.1101/gr.197046.115
PMID: 26755635
قاعدة البيانات: MEDLINE
الوصف
تدمد:1549-5469
DOI:10.1101/gr.197046.115