A Photoredox Reaction for the Selective Modification of 5-Carboxycytosine in DNA.

Covalent epigenetic modifications contribute to the regulation of important cellular processes during development and differentiation, and changes in their genomic distribution and frequency are linked to the emergence of genetic disease states. Chemical and enzymatic methods that selectively target the orthogonal chemical functionality of epigenetic markers are central to the study of their distribution and function, and considerable research effort has been focused on the development of nondestructive sequencing approaches which preserve valuable DNA samples. Photoredox catalysis enables transformations with tunable chemoselectivity under mild, biocompatible reaction conditions. We report the reductive decarboxylation of 5-carboxycytosine via a novel iridium-based treatment, which represents the first application of visible-light photochemistry to epigenetic sequencing via direct base conversion. We propose that the reaction involves an oxidative quenching cycle beginning with single-electron reduction of the nucleobase by the photocatalyst, followed by hydrogen atom transfer from a thiol. The saturation of the C5-C6 backbone permits decarboxylation of the nonaromatic intermediate, and hydrolysis of the N4-amine constitutes a conversion from a cytosine derivative to a T-like base. This conversion demonstrates selectivity for 5-carboxycytosine over other canonical or modified nucleoside monomers, and is thereby applied to the sequencing of 5-carboxycytosine within modified oligonucleotides. The photochemistry explored in this study can also be used in conjunction with enzymatic oxidation by TET to profile 5-methylcytosine at single-base resolution. Compared to other base-conversion treatments, the rapid photochemical reaction takes place within minutes, which could provide advantages for high-throughput detection and diagnostic applications.

A DddA ortholog-based and transactivator-assisted nuclear and mitochondrial cytosine base editors with expanded target compatibility.

Bacterial double-stranded DNA (dsDNA) cytosine deaminase DddAtox-derived cytosine base editor (DdCBE) and its evolved variant, DddA11, guided by transcription-activator-like effector (TALE) proteins, enable mitochondrial DNA (mtDNA) editing at TC or HC (H = A, C, or T) sequence contexts, while it remains relatively unattainable for GC targets. Here, we identified a dsDNA deaminase originated from a Roseburia intestinalis interbacterial toxin (riDddAtox) and generated CRISPR-mediated nuclear DdCBEs (crDdCBEs) and mitochondrial CBEs (mitoCBEs) using split riDddAtox, which catalyzed C-to-T editing at both HC and GC targets in nuclear and mitochondrial genes. Moreover, transactivator (VP64, P65, or Rta) fusion to the tail of DddAtox- or riDddAtox-mediated crDdCBEs and mitoCBEs substantially improved nuclear and mtDNA editing efficiencies by up to 3.5- and 1.7-fold, respectively. We also used riDddAtox-based and Rta-assisted mitoCBE to efficiently stimulate disease-associated mtDNA mutations in cultured cells and in mouse embryos with conversion frequencies of up to 58% at non-TC targets.

Increased mutation and gene conversion within human segmental duplications.

Single-nucleotide variants (SNVs) in segmental duplications (SDs) have not been systematically assessed because of the limitations of mapping short-read sequencing data1,2. Here we constructed 1:1 unambiguous alignments spanning high-identity SDs across 102 human haplotypes and compared the pattern of SNVs between unique and duplicated regions3,4. We find that human SNVs are elevated 60% in SDs compared to unique regions and estimate that at least 23% of this increase is due to interlocus gene conversion (IGC) with up to 4.3 megabase pairs of SD sequence converted on average per human haplotype. We develop a genome-wide map of IGC donors and acceptors, including 498 acceptor and 454 donor hotspots affecting the exons of about 800 protein-coding genes. These include 171 genes that have 'relocated' on average 1.61 megabase pairs in a subset of human haplotypes. Using a coalescent framework, we show that SD regions are slightly evolutionarily older when compared to unique sequences, probably owing to IGC. SNVs in SDs, however, show a distinct mutational spectrum: a 27.1% increase in transversions that convert cytosine to guanine or the reverse across all triplet contexts and a 7.6% reduction in the frequency of CpG-associated mutations when compared to unique DNA. We reason that these distinct mutational properties help to maintain an overall higher GC content of SD DNA compared to that of unique DNA, probably driven by GC-biased conversion between paralogous sequences5,6.

DNA methylation and gene expression changes in mouse mammary tissue during successive lactations: part II - the impact of lactation rank.

Mastitis is among the main reasons women cease breastfeeding. In farm animals, mastitis results in significant economic losses and the premature culling of some animals. Nevertheless, the effect of inflammation on the mammary gland is not completely understood. This article discusses the changes to DNA methylation in mouse mammary tissue caused by lipopolysaccharide-induced inflammation after in vivo intramammary challenges and the differences in DNA methylation between 1st and 2nd lactations. Lactation rank induces 981 differential methylations of cytosines (DMCs) in mammary tissue. Inflammation in 1st lactation compared to inflammation in 2nd lactation results in the identification of 964 DMCs. When comparing inflammation in 1st vs. 2nd lactations with previous inflammation history, 2590 DMCs were identified. Moreover, Fluidigm PCR data show changes in the expression of several genes related to mammary function, epigenetic regulation, and the immune response. We show that the epigenetic regulation of two successive physiological lactations is not the same in terms of DNA methylation and that the effect of lactation rank on DNA methylation is stronger than that of the onset of inflammation. The conditions presented here show that few DMCs are shared between comparisons, suggesting a specific epigenetic response depending on lactation rank, the presence of inflammation, and even whether the cells had previously suffered inflammation. In the long term, this information could lead to a better understanding of the epigenetic regulation of lactation in both physiological and pathological conditions.Abbreviations: RRBS, reduced representation bisulphite sequencing; RT-qPCR, real-time quantitative polymerase chain reaction; MEC, mammary epithelial cells; MaSC, mammary stem cell; TSS, transcription start site; TTS, transcription termination site; UTR, untranslated region; SINE, short interspersed nuclear element; LINE, long interspersed nuclear element; CGI, CpG island; DEG, differentially expressed gene; DMC, differentially methylated cytosine; DMR, differentially methylated region; GO term, gene ontology term; MF, molecular function; BP, biological process.

Gene editing and scalable functional genomic screening in Leishmania species using the CRISPR/Cas9 cytosine base editor toolbox LeishBASEedit.

CRISPR/Cas9 gene editing has revolutionised loss-of-function experiments in Leishmania, the causative agent of leishmaniasis. As Leishmania lack a functional non-homologous DNA end joining pathway however, obtaining null mutants typically requires additional donor DNA, selection of drug resistance-associated edits or time-consuming isolation of clones. Genome-wide loss-of-function screens across different conditions and across multiple Leishmania species are therefore unfeasible at present. Here, we report a CRISPR/Cas9 cytosine base editor (CBE) toolbox that overcomes these limitations. We employed CBEs in Leishmania to introduce STOP codons by converting cytosine into thymine and created http://www.leishbaseedit.net/ for CBE primer design in kinetoplastids. Through reporter assays and by targeting single- and multi-copy genes in L. mexicana, L. major, L. donovani, and L. infantum, we demonstrate how this tool can efficiently generate functional null mutants by expressing just one single-guide RNA, reaching up to 100% editing rate in non-clonal populations. We then generated a Leishmania-optimised CBE and successfully targeted an essential gene in a plasmid library delivered loss-of-function screen in L. mexicana. Since our method does not require DNA double-strand breaks, homologous recombination, donor DNA, or isolation of clones, we believe that this enables for the first time functional genetic screens in Leishmania via delivery of plasmid libraries.

Synthesis and properties of PNA containing a dicationic nucleobase based on N4-benzoylated cytosine.

We report the synthesis of a peptide nucleic acid (PNA) monomer containing N4-bis(aminomethyl)benzoylated cytosine (BzC2+ base). The BzC2+ monomer was incorporated into PNA oligomers using Fmoc-based solid-phase synthesis. The BzC2+ base in PNA had two positive charges and exhibited greater affinity for DNA G base than the natural C base. The BzC2+ base stabilized PNA-DNA heteroduplexes through electrostatic attractions, even in high salt conditions. The two positive charges on the BzC2+ residue did not compromise the sequence specificity of PNA oligomers. These insights will aid the future design of cationic nucleobases.

i2OM: Toward a better prediction of 2'-O-methylation in human RNA.

2'-O-methylation (2OM) is an omnipresent post-transcriptional modification in RNAs. It is important for the regulation of RNA stability, mRNA splicing and translation, as well as innate immunity. With the increase in publicly available 2OM data, several computational tools have been developed for the identification of 2OM sites in human RNA. Unfortunately, these tools suffer from the low discriminative power of redundant features, unreasonable dataset construction or overfitting. To address those issues, based on four types of 2OM (2OM-adenine (A), cytosine (C), guanine (G), and uracil (U)) data, we developed a two-step feature selection model to identify 2OM. For each type, the one-way analysis of variance (ANOVA) combined with mutual information (MI) was proposed to rank sequence features for obtaining the optimal feature subset. Subsequently, four predictors based on eXtreme Gradient Boosting (XGBoost) or support vector machine (SVM) were presented to identify the four types of 2OM sites. Finally, the proposed model could produce an overall accuracy of 84.3 % on the independent set. To provide a convenience for users, an online tool called i2OM was constructed and can be freely access at i2om.lin-group.cn. The predictor may provide a reference for the study of the 2OM.

Detection of CpG methylation level using methyl-CpG-binding domain-fused fluorescent protein.

Methylation of cytosine to 5-methylcytosine on CpG dinucleotides is the most frequently studied epigenetic modification involved in the regulation of gene expression. In normal tissues, tissue-specific CpG methylation patterns are established during development. In contrast, alterations in methylation patterns have been observed in abnormal cells, such as cancer cells. Cancer type-specific CpG methylation patterns have been identified and used as biomarkers for cancer diagnosis. In this study, we developed a hybridization-based CpG methylation level sensing system using a methyl-CpG-binding domain (MBD)-fused fluorescent protein. In this system, the target DNA is captured by a complementary methylated probe DNA. When the target DNA is methylated, a symmetrically methylated CpG is formed in the double-stranded DNA. MBD specifically recognizes symmetrical methyl-CpG on double-stranded DNA; therefore, the methylation level is quantified by measuring the fluorescence intensity of the bound MBD-fused fluorescent protein. We prepared MBD-fused AcGFP1 and quantified the CpG methylation levels of the target DNA against SEPT9, BRCA1, and long interspersed nuclear element-1 (LINE-1) using MBD-AcGFP1. This detection principle can be applied to the simultaneous and genome-wide modified base detection systems using microarrays coupled with modified base binding proteins fused to fluorescent proteins.

Optimization of Cas9 activity through the addition of cytosine extensions to single-guide RNAs.

The precise regulation of the activity of Cas9 is crucial for safe and efficient editing. Here we show that the genome-editing activity of Cas9 can be constrained by the addition of cytosine stretches to the 5'-end of conventional single-guide RNAs (sgRNAs). Such a 'safeguard sgRNA' strategy, which is compatible with Cas12a and with systems for gene activation and interference via CRISPR (clustered regularly interspaced short palindromic repeats), leads to the length-dependent inhibition of the formation of functional Cas9 complexes. Short cytosine extensions reduced p53 activation and cytotoxicity in human pluripotent stem cells, and enhanced homology-directed repair while maintaining bi-allelic editing. Longer extensions further decreased on-target activity yet improved the specificity and precision of mono-allelic editing. By monitoring indels through a fluorescence-based allele-specific system and computational simulations, we identified optimal windows of Cas9 activity for a number of genome-editing applications, including bi-allelic and mono-allelic editing, and the generation and correction of disease-associated single-nucleotide substitutions via homology-directed repair. The safeguard-sgRNA strategy may improve the safety and applicability of genome editing.

Stretching effects on non-adiabatic electron dynamic behavior in poly(dG)-poly(dC) DNA upon the proton irradiation.

The electronic excitations caused by DNA when exposed to ion radiation is essential to DNA damage. In this paper, we investigated the energy deposition and electron excitation process of DNA with reasonable stretching range upon proton irradiation based on time-dependent density functional theory. Stretching changes the strength of hydrogen bonding between the DNA base pairs, which in turn affects the Coulomb interaction between the projectile and DNA. As a semi-flexible molecule, the way of energy deposition is weakly sensitive to the stretching rate of DNA. However, the increase of stretching rate causes the increase of charge density along the trajectory channel, sequentially resulting in an increase in proton resistance along the intruding channel. The Mulliken charge analysis indicates that the guanine base and guanine ribose are ionized, meanwhile the cytosine base and cytosine ribose are reduced at all stretching rates. In a few femtoseconds, there exists an electron flow passing through the guanine ribose, guanine, cytosine base and the cytosine ribose in turn. This electron flow increases electron transfer and DNA ionization, promoting the side chain damage of the DNA upon ion irradiation. Our results provide a theoretical insight for deciphering the physical mechanism of the early stage of the irradiation process, and are also of great significance for the study of particle beam cancer therapy in different biological tissues.

Nucleobase Specific Understanding about the Interaction of Antimalarial Drug Chloroquine with Duplex DNA.

Antimalarial action of a drug is closely associated with the interaction with the parasite's DNA. Hence, in this study, the interaction of an important antimalarial drug, chloroquine (CLQ), has been investigated with six different sequences of DNA having pure adenine (A)-thymine (T) and pure cytosine (C)-guanine (G) as well as mixed nucleobases to achieve the nucleobase level of information in the binding of antimalarial drug with DNA along with binding induced stabilization/destabilization of DNA using different spectroscopic methods and molecular dynamics simulation technique. Further, the experiments have been also performed with 4-amino-7-chloroquinoline (7CLQ), an analogue of CLQ, to understand the role of the quinoline ring and side chain of CLQ in the binding with different sequences of DNA. The binding efficiency of CLQ with any sequence of DNA is higher than 7CLQ suggesting that the presence of charge on CLQ plays a prominent role in DNA binding. The data suggest that the binding of drug as well as induced stabilization of DNA depends significantly on the nature as well as the arrangement of the nucleobases. In general, the binding of CLQ with pure CG DNA is higher than with pure AT DNA; moreover, it prefers an alternate order of CG/AT than continual nucleobases in duplex DNA. CLQ predominately accommodates in the minor groove of AT DNA and prefers to form hydrogen bond mostly with the adenine nucleobase. In contrast to AT DNA, CLQ intrudes into the both major and minor grooves, but it is primarily accommodated into the major groove of CG DNA. CLQ forms a hydrogen bond mainly with guanine in the major groove and cytosine in the minor groove of CG DNA which enhances the binding of CLQ compared to AT DNA as well as induces higher stabilization in CG DNA. The molecular level information obtained about the functional group responsible for the interaction of CLQ as well as the role of chemical nature of nucleobases along with its ordering on the binding of CLQ with DNA may be useful in comprehensive understanding of its action mechanism.

Cytosine methylation in GABA B1 receptor identifies alcohol-related changes for men in blood and brain tissues.

AIMS: Alcohol use alters the reward signaling processes contributing to the development of addiction. We studied the effects of alcohol use disorder (AUD) on brain regions and blood of deceased women and men to examine sex-dependent differences in epigenetic changes associated with AUD. We investigated the effects of alcohol use on the gene promoter methylation of GABBR1 coding for GABAB receptor subunit 1 in blood and brain. METHODS: We chose six brain regions associated with addiction and the reward pathway (nucleus arcuatus, nucleus accumbens, the mamillary bodies, amygdala, hippocampus and anterior temporal cortex) and performed epigenetic profiling of the proximal promoter of the GABBR1 gene of post-mortem brain and blood samples of 17 individuals with AUD pathology (4 female, 13 male) and 31 healthy controls (10 female, 21 male). RESULTS: Our results show sex-specific effects of AUD on GABBR1 promoter methylation. Especially, CpG -4 showed significant tissue-independent changes and significantly decreased methylation levels for the AUD group in the amygdala and the mammillary bodies of men. We saw prominent and consistent change in CpG-4 across all investigated tissues. For women, no significant loci were observed. CONCLUSION: We found sex-dependent differences in GABBR1 promoter methylation in relation to AUD. CpG-4 hypomethylation in male individuals with AUD is consistent for most brain regions. Blood shows similar results without reaching significance, potentially serving as a peripheral marker for addiction-associated neuronal adaptations. Further research is needed to discover more contributing factors in the pathological alterations of alcohol addiction to offer sex-specific biomarkers and treatment.

Spontaneous deamination of cytosine to uracil is biased to the non-transcribed DNA strand in yeast.

Transcription in Saccharomyces cerevisiae is associated with elevated mutation and this partially reflects enhanced damage of the corresponding DNA. Spontaneous deamination of cytosine to uracil leads to CG>TA mutations that provide a strand-specific read-out of damage in strains that lack the ability to remove uracil from DNA. Using the CAN1 forward mutation reporter, we found that C>T and G>A mutations, which reflect deamination of the non-transcribed and transcribed DNA strands, respectively, occurred at similar rates under low-transcription conditions. By contrast, the rate of C>T mutations was 3-fold higher than G>A mutations under high-transcription conditions, demonstrating biased deamination of the non-transcribed strand (NTS). The NTS is transiently single-stranded within the ∼15 bp transcription bubble, or a more extensive region of the NTS can be exposed as part of an R-loop that can form behind RNA polymerase. Neither the deletion of genes whose products restrain R-loop formation nor the over-expression of RNase H1, which degrades R-loops, reduced the biased deamination of the NTS, and no transcription-associated R-loop formation at CAN1 was detected. These results suggest that the NTS within the transcription bubble is a target for spontaneous deamination and likely other types of DNA damage.

The DNA cytosine methylome revealed two methylation motifs in the upstream regions of genes related to morphological and physiological differentiation in Streptomyces coelicolor A(3)2 M145.

DNA methylation is an epigenetic modification detected in both prokaryotic and eukaryotic genomic DNAs. In bacteria, the importance of 5-methylcytosine (m5C) in gene expression has been less investigated than in eukaryotic systems. Through dot-blot analysis employing m5C antibodies against chromosomal DNA, we have previously demonstrated that m5C influences the differentiation of Streptomyces coelicolor A(3)2 M145 in solid sporulating and liquid non-sporulating complex media. Here, we mapped the methylated cytosines of the M145 strain growing in the defined Maltose Glutamate (MG) liquid medium. Sequencing of the M145 genome after bisulfite treatment (BS-sequencing) evidenced 3360 methylated cytosines and the two methylation motifs, GGCmCGG and GCCmCG, in the upstream regions of 321 genes. Besides, the role of cytosine methylation was investigated using the hypo-methylating agent 5'-aza-2'-deoxycytidine (5-aza-dC) in S. coelicolor cultures, demonstrating that m5C affects both growth and antibiotic biosynthesis. Finally, quantitative reverse-transcription polymerase-chain-reaction (RT-qPCR) analysis of genes containing the methylation motifs in the upstream regions showed that 5-aza-dC treatment influenced their transcriptional levels and those of the regulatory genes for two antibiotics. To the best of our knowledge, this is the first study that reports the cytosine methylome of S. coelicolor M145, supporting the crucial role ascribed to cytosine methylation in controlling bacterial gene expression.

Transgressive and parental dominant gene expression and cytosine methylation during seed development in Brassica napus hybrids.

KEY MESSAGE: Transcriptomic and epigenomic profiling of gene expression and small RNAs during seed and seedling development reveals expression and methylation dominance levels with implications on early stage heterosis in oilseed rape. The enhanced performance of hybrids through heterosis remains a key aspect in plant breeding; however, the underlying mechanisms are still not fully elucidated. To investigate the potential role of transcriptomic and epigenomic patterns in early expression of hybrid vigor, we investigated gene expression, small RNA abundance and genome-wide methylation in hybrids from two distant Brassica napus ecotypes during seed and seedling developmental stages using next-generation sequencing. A total of 31117, 344, 36229 and 7399 differentially expressed genes, microRNAs, small interfering RNAs and differentially methylated regions were identified, respectively. Approximately 70% of the differentially expressed or methylated features displayed parental dominance levels where the hybrid followed the same patterns as the parents. Via gene ontology enrichment and microRNA-target association analyses during seed development, we found copies of reproductive, developmental and meiotic genes with transgressive and paternal dominance patterns. Interestingly, maternal dominance was more prominent in hypermethylated and downregulated features during seed formation, contrasting to the general maternal gamete demethylation reported during gametogenesis in angiosperms. Associations between methylation and gene expression allowed identification of putative epialleles with diverse pivotal biological functions during seed formation. Furthermore, most differentially methylated regions, differentially expressed siRNAs and transposable elements were in regions that flanked genes without differential expression. This suggests that differential expression and methylation of epigenomic features may help maintain expression of pivotal genes in a hybrid context. Differential expression and methylation patterns during seed formation in an F1 hybrid provide novel insights into genes and mechanisms with potential roles in early heterosis.

Dynamics of RNA m5C modification during brain development.

Post-transcriptional RNA modifications have been recognized as key regulators of neuronal differentiation and synapse development in the mammalian brain. While distinct sets of 5-methylcytosine (m5C) modified mRNAs have been detected in neuronal cells and brain tissues, no study has been performed to characterize methylated mRNA profiles in the developing brain. Here, together with regular RNA-seq, we performed transcriptome-wide bisulfite sequencing to compare RNA cytosine methylation patterns in neural stem cells (NSCs), cortical neuronal cultures, and brain tissues at three postnatal stages. Among 501 m5C sites identified, approximately 6% are consistently methylated across all five conditions. Compared to m5C sites identified in NSCs, 96% of them were hypermethylated in neurons and enriched for genes involved in positive transcriptional regulation and axon extension. In addition, brains at the early postnatal stage demonstrated substantial changes in both RNA cytosine methylation and gene expression of RNA cytosine methylation readers, writers, and erasers. Furthermore, differentially methylated transcripts were significantly enriched for genes regulating synaptic plasticity. Altogether, this study provides a brain epitranscriptomic dataset as a new resource and lays the foundation for further investigations into the role of RNA cytosine methylation during brain development.

Antibody-free photoelectrochemical biosensor for DNA carboxylation detection based on SnS2@Ti3C2 heterojunction.

As an important epigenetic modification, 5-carboxycytosine (5caC) played an important role in gene regulation, cell differentiation and growth. 5caC existed in many cells and tissues, but it was highly similar to the structure of other cytosine derivatives and had less content in the genome. Therefore, it was urgent to develop a sensitive and highly selective trace biosensor to detect 5caC. A novel photoelectrochemical biosensor was fabricated for 5-carboxy-2'-deoxycytidine-5'-triphosphate (5cadCTP) detection, where SnS2@Ti3C2 nanocomposite was employed as photoactive material, polyethyleneimine was used as 5cadCTP recognition and capture reagent, and Ru(NH3)63+ was used as photosensitizer for signal amplification. Due the good conductivity of Ti3C2 MXene and the matched energy band between Ti3C2 MXene and SnS2, SnS2@Ti3C2 nanocomposite presented strong photoactivity, which was beneficial to the high detection sensitivity. For specific recognition of 5cadCTP, the covalent interaction of -NH2 in 5cadCTP with -COOH on the substrate electrode was used, which was beneficial to the high detection selectivity. A broad linear relationship between photocurrent and 5cadCTP concentration was observed ranging from 1 pM to 0.2 µM. The low detection limit of 260 fM was achieved. The developed method has high detection specificity and can even distinguish 5caC with its derivatives. In addition, the applicability was evaluated by detecting the content change of 5caC in the genomic DNA of rice seedlings after cultured with environmental pollutants. This work provides a novel platform for 5cadCTP detection, and it can also be applied to detect other cytosine derivatives with suitable recognition strategies.

Electron Attachment to DNA: The Protective Role of Amino Acids.

We have studied the effect of amino acids on the electron attachment properties of a DNA nucleobase, with cytosine as a model system. The equation of motion coupled cluster theory with an extended basis set has been used to simulate the electron-attached state of the DNA model system. Arginine, alanine, lysine, and glycine are the four amino acids considered to investigate their role in electron attachment to a DNA nucleobase. The electron attachment to cytosine in all the four cytosine-amino acid gas-phase dimer complexes follows a doorway mechanism, where the electron gets transferred from the initial dipole-bound doorway state to the final nucleobase-bound state through the mixing of electronic and nuclear degrees of freedom. When cytosine is bulk-solvated with glycine, the glycine-bound state acts as the doorway state, where the initial electron density is localized on the bulk amino acid and away from the nucleobase, thus leading to the physical shielding of the nucleobase from the incoming electron. At the same time, the presence of amino acids can increase the stability of the nucleobase-bound anionic state, which can suppress the sugar-phosphate bond rupture caused by dissociative electron attachment to DNA.

The dynamical temporal behaviors of guanine-cytosine coherent charge transfer.

The vibrational coupling between the nucleus and electrons is an important factor in determining the ultrafast charge transfer rate of DNA biological systems. However, in most typical DNA base pairs like the guanine-cytosine (G-C) base pair, the vibrational coupling of ultrafast coherent charge transfer has been largely ignored. Here, we simulate the nucleus-electron interaction in the coherent charge transfer of G-C using ab initio molecular dynamics and Ehrenfest dynamics. Interestingly, the charge separation of G-C exhibits clear periodic oscillations. The calculated molecular orbitals, non-covalent interactions, and transition density matrix have oscillations with a period of about 10 fs. The reason behind G-C coherent ultrafast charge transfer is elucidated by examining the regular fluctuations evolving with time of the electron coupling strength, reorganization energy, and free energy. Our research can be extended to longer sequences of biological bases, contributing to the design of flexible, lightweight, and efficient biological DNA detection devices.