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DNA Editing by APOBECs: A Genomic Preserver and Transformer

Published on Jan 1, 2016in Trends in Genetics10.627
· DOI :10.1016/j.tig.2015.10.005
Binyamin A. Knisbacher9
Estimated H-index: 9
(BIU: Bar-Ilan University),
Doron Gerber21
Estimated H-index: 21
(BIU: Bar-Ilan University),
Erez Y. Levanon33
Estimated H-index: 33
(BIU: Bar-Ilan University)
Sources
Abstract
Information warfare is not limited to the cyber world because it is waged within our cells as well. The unique AID (activation-induced cytidine deaminase)/APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide) family comprises proteins that alter DNA sequences by converting deoxycytidines to deoxyuridines through deamination. This C-to-U DNA editing enables them to inhibit parasitic viruses and retrotransposons by disrupting their genomic content. In addition to attacking genomic invaders, APOBECs can target their host genome, which can be beneficial by initiating processes that create antibody diversity needed for the immune system or by accelerating the rate of evolution. AID can also alter gene regulation by removing epigenetic modifications from genomic DNA. However, when uncontrolled, these powerful agents of change can threaten genome stability and eventually lead to cancer.
  • References (144)
  • Citations (38)
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References144
Newest
#1Binyamin A. Knisbacher (BIU: Bar-Ilan University)H-Index: 9
#2Erez Y. Levanon (BIU: Bar-Ilan University)H-Index: 33
Long terminal repeat retrotransposons (LTR) are widespread in vertebrates and their dynamism facilitates genome evolution. However, these endogenous retroviruses (ERVs) must be restricted to maintain genomic stability. The APOBECs, a protein family that can edit C-to-U in DNA, do so by interfering with reverse transcription and hypermutating retrotransposon DNA. In some cases, a retrotransposon may integrate into the genome despite being hypermutated. Such an event introduces a unique sequence i...
17 CitationsSource
#1Kin Chan (NIH: National Institutes of Health)H-Index: 8
#2Steven A. Roberts (WSU: Washington State University)H-Index: 24
Last. Dmitry A. Gordenin (NIH: National Institutes of Health)H-Index: 45
view all 12 authors...
Dmitry Gordenin and colleagues use a yeast reporter strain to identify distinct mutagenic signatures for the cytosine deaminases APOBEC3A and APOBEC3B. They find that cancer samples with APOBEC3A-like mutation signatures have greater than tenfold more APOBEC signature mutations than those with APOBEC3B-like signatures.
130 CitationsSource
#1Charles Swanton (Francis Crick Institute)H-Index: 66
#2Nicholas McGranahan (UCL: University College London)H-Index: 31
Last. Reuben S. Harris (UMN: University of Minnesota)H-Index: 59
view all 4 authors...
Deep sequencing technologies are revealing the complexities of cancer evolution, casting light on mutational processes fueling tumor adaptation, immune escape, and treatment resistance. Understanding mechanisms driving cancer diversity is a critical step toward developing strategies to attenuate tumor evolution and adaptation. One emerging mechanism fueling tumor diversity and subclonal evolution is genomic DNA cytosine deamination catalyzed by APOBEC3B and at least one other APOBEC family membe...
145 CitationsSource
#1Stephen Henderson (UCL: University College London)H-Index: 30
#2Tim Fenton (UCL: University College London)H-Index: 22
The APOBEC3 cytosine deaminases play key roles in innate immunity through their ability to mutagenize viral DNA and restrict viral replication. Recent advances in cancer genomics, together with biochemical characterization of the APOBEC3 enzymes, have now implicated at least two family members in somatic mutagenesis during tumor development. We review the evidence linking these enzymes to carcinogenesis and highlight key questions, including the potential mechanisms that misdirect APOBEC3 activi...
40 CitationsSource
#1Reuben S. Harris (UMN: University of Minnesota)H-Index: 59
#2Jaquelin P. DudleyH-Index: 24
147 CitationsSource
#1Stefan RebhandlH-Index: 7
#2Michael HuemerH-Index: 7
Last. Roland GeisbergerH-Index: 8
view all 4 authors...
Mutations are the basis for evolution and the development of genetic diseases. Especially in cancer, somatic mutations in oncogenes and tumor suppressor genes alongside the occurrence of passenger mutations have been observed by recent deep-sequencing approaches. While mutations have long been considered random events induced by DNA-replication errors or by DNA damaging agents, genome sequencing led to the discovery of non-random mutation signatures in many human cancer. Common non-random mutati...
53 CitationsSource
#1Shraddha Sharma (Roswell Park Cancer Institute)H-Index: 6
#2Santosh K. Patnaik (Roswell Park Cancer Institute)H-Index: 14
Last. Bora E. Baysal (Roswell Park Cancer Institute)H-Index: 31
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Aberrant RNA editing is linked to a range of neuropsychiatric and chronic diseases. Here Sharma et al. show that APOBEC3A can function as an RNA editing protein in response to physiological stimuli, significantly expanding our understanding of RNA editing and the role this may play in diseases.
73 CitationsSource
#1Binyamin A. Knisbacher (BIU: Bar-Ilan University)H-Index: 9
#2Erez Y. Levanon (BIU: Bar-Ilan University)H-Index: 33
Genome evolution is commonly viewed as a gradual process that is driven by random mutations that accumulate over time. However, DNA- and RNA-editing enzymes have been identified that can accelerate evolution by actively modifying the genomically encoded information. The apolipoprotein B mRNA editing enzymes, catalytic polypeptide-like (APOBECs) are potent restriction factors that can inhibit retroelements by cytosine-to-uridine editing of retroelement DNA after reverse transcription. In some cas...
12 CitationsSource
#1Gabriele B. Beck-Engeser (UCSF: University of California, San Francisco)H-Index: 11
#2Rebecca Winkelmann (FAU: University of Erlangen-Nuremberg)H-Index: 4
Last. Matthias Wabl (UCSF: University of California, San Francisco)H-Index: 38
view all 13 authors...
In general, a long-lasting immune response to viruses is achieved when they are infectious and replication-competent. In the mouse, the neutralizing antibody response to Friend murine leukemia virus is contributed by an allelic form of the enzyme Apobec3 (abbreviated A3). This is counterintuitive, because A3 directly controls viremia before the onset of adaptive anti-viral immune responses. It suggests that A3 also affects the antibody response directly. Here we studied the relative size of cell...
6 CitationsSource
#1Almudena R. Ramiro (Centro Nacional de Investigaciones Cardiovasculares)H-Index: 24
#2Vasco M. Barreto (IGC: Instituto Gulbenkian de Ciência)H-Index: 13
The regulation of demethylation in vertebrates has begun to be elucidated in the past decade. However, a possible involvement of activation-induced cytidine deaminase (AID) in this process remains uncertain. We survey the data supporting or casting doubt on such a role, and propose that there is no strong evidence for an involvement of AID in genome-wide active demethylation processes. Conversely, we present evidence that favors AID involvement in gene-specific demethylation events underlying ce...
28 CitationsSource
Cited By38
Newest
#1Hisashi Takei (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 9
#2Hirofumi Fukuda (Kyoto University)H-Index: 1
Last. Keisuke Shindo (Kyoto University)H-Index: 15
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The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) protein family members have cytidine deaminase activity and can induce cytosine to uracil transition in nucleic acid. The main function of APOBEC3 (A3) proteins is to trigger an innate immune response to viral infections. Recent reports have shown that several APOBEC family proteins such as A3B can induce somatic mutations into genomic DNA and thus promote cancer development. However, the role of A3D on somatic mutation...
Source
Abstract Human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS). Novel strategies to combat this pandemic include the discovery of cellular proteins targeting distinct steps of the HIV replication cycle. Here, we summarize our current knowledge on antiviral proteins interfering with the infectivity of released HIV particles.
Source
#1Cody P. Diamond (MUN: Memorial University of Newfoundland)
#2Junbum Im (MUN: Memorial University of Newfoundland)
Last. Mani Larijani (SFU: Simon Fraser University)
view all 12 authors...
Abstract Background AID/APOBEC3 (A3) enzymes instigate genomic mutations that are involved in immunity and cancer. Although they can deaminate any deoxycytidine (dC) to deoxyuridine (dU), each family member has a signature preference determined by nucleotides surrounding the target dC. This WR C (W = A/T, R = A/G) and Y C (Y = T/C) hotspot preference is established for AID and A3A/A3B, respectively. Base alkylation and oxidation are two of the most common types of DNA damage induced environmenta...
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#1Jessica Stewart (WSU: Wayne State University)H-Index: 1
#2Thomas C. Holland (WSU: Wayne State University)H-Index: 10
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APOBEC3 family of DNA-cytosine deaminases inactivate and mutate several human viruses. We constructed a human cell line that is inducible for EGFP-tagged APOBEC3A and found A3A predominantly in the nuclei. When these cells were infected with Herpes Simplex Virus-1, virus titer was unaffected by A3A expression despite nuclear virus replication. When A3A expression and virus infection were monitored, A3A was found predominantly to be nuclear in infected cells up to 3 h post-infection, but was pred...
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#1Theodoulakis Christofi (European University Cyprus)H-Index: 1
#2Apostolos Zaravinos (European University Cyprus)H-Index: 26
Post-transcriptional modifications have been recently expanded with the addition of RNA editing, which is predominantly mediated by adenosine and cytidine deaminases acting on DNA and RNA. Here, we review the full spectrum of physiological processes in which these modifiers are implicated, among different organisms. Adenosine to inosine (A-to-I) editors, members of the ADAR and ADAT protein families are important regulators of alternative splicing and transcriptional control. On the other hand, ...
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The therapeutic effects of gene therapy using adeno-associated virus (AAV) vectors are dependent on the efficacy of viral transduction. Currently, we have reached the safe limits of AAV vector dose, beyond which damaging inflammatory responses are seen. To improve the efficacy of AAV transduction, we treated mouse embryonic fibroblasts, primate retinal pigment epithelial cells, and human retinal explants with hydroxychloroquine (HCQ) 1 h prior to transduction with an AAV2 vector encoding GFP dri...
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#1Ganna Galitska (UNITO: University of Turin)H-Index: 2
#2Matteo Biolatti (UNITO: University of Turin)H-Index: 5
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#1Xiongxiong Li (Pasteur Institute)
#2Vincent Caval (Pasteur Institute)H-Index: 6
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The incidence of developing cancer should increase with the body mass, yet is not the case, a conundrum referred to as Peto’s paradox. Elephants have a lower incidence of cancer suggesting that these animals have probably evolved different ways to protect themselves against the disease. The paradox is worth revisiting with the realization that most mammals encode an endogenous APOBEC3 cytidine deaminase capable of mutating single stranded DNA. Indeed, the mutagenic activity of some APOBEC3 enzym...
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#1Zhuyun Bian (Purdue University)H-Index: 2
#2Yajia Ni (NWAFU: Northwest A&F University)H-Index: 1
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A-to-I RNA editing is an important post-transcriptional modification that converts adenosine (A) to inosine (I) in RNA molecules via hydrolytic deamination. Although editing of mRNAs catalyzed by adenosine deaminases acting on RNA (ADARs) is an evolutionarily conserved mechanism in metazoans, organisms outside the animal kingdom lacking ADAR orthologs were thought to lack A-to-I mRNA editing. However, recent discoveries of genome-wide A-to-I mRNA editing during the sexual stage of the wheat scab...
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Numerous human diseases arise from alterations of genetic information, most notably DNA mutations. Thought to be merely the intermediate between DNA and protein, changes in RNA sequence were an afterthought until the discovery of RNA editing thirty years ago. RNA editing alters RNA sequence without altering the sequence or integrity of genomic DNA. The most common RNA editing events are A-to-I changes mediated by adenosine deaminase acting on RNA (ADAR), and C-to-U editing mediated by apolipopro...
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