DNA Repair最新文献

{"title":"What are the DNA lesions underlying formaldehyde toxicity?","authors":"Bente Benedict,&nbsp;Stella Munkholm Kristensen,&nbsp;Julien P. Duxin","doi":"10.1016/j.dnarep.2024.103667","DOIUrl":"10.1016/j.dnarep.2024.103667","url":null,"abstract":"<div><p>Formaldehyde is a highly reactive organic compound. Humans can be exposed to exogenous sources of formaldehyde, but formaldehyde is also produced endogenously as a byproduct of cellular metabolism. Because formaldehyde can react with DNA, it is considered a major endogenous source of DNA damage. However, the nature of the lesions underlying formaldehyde toxicity in cells remains vastly unknown. Here, we review the current knowledge of the different types of nucleic acid lesions that are induced by formaldehyde and describe the repair pathways known to counteract formaldehyde toxicity. Taking this knowledge together, we discuss and speculate on the predominant lesions generated by formaldehyde, which underly its natural toxicity.</p></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"138 ","pages":"Article 103667"},"PeriodicalIF":3.8,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140097879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deletions initiated by the vaccinia virus TopIB protein in yeast","authors":"Jang Eun Cho ,&nbsp;Samantha Shaltz ,&nbsp;Lyudmila Yakovleva ,&nbsp;Stewart Shuman ,&nbsp;Sue Jinks-Robertson","doi":"10.1016/j.dnarep.2024.103664","DOIUrl":"10.1016/j.dnarep.2024.103664","url":null,"abstract":"<div><p>The type IB topoisomerase of budding yeast (yTop1) generates small deletions in tandem repeats through a sequential cleavage mechanism and larger deletions with random endpoints through the nonhomologous end-joining (NHEJ) pathway. Vaccinia virus Top1 (vTop1) is a minimized version of the eukaryal TopIB enzymes and uniquely has a strong consensus cleavage sequence: the pentanucleotide (T/C)CCTTp↓. To define the relationship between the position of TopIB cleavage and mutagenic outcomes, we expressed vTop1 in yeast <em>top1</em>Δ strains containing reporter constructs with a single CCCTT site, tandem CCCTT sites, or CCCTT sites separated by 42 bp. vTop1 cleavage at a single CCCTT site was associated with small, NHEJ-dependent deletions. As observed with yTop1, vTop1 generated 5-bp deletions at tandem CCCTT sites. In contrast to yTop1-initiated deletions, however, 5-bp deletions associated with vTop1 expression were not affected by the level of ribonucleotides in genomic DNA. vTop1 expression was associated with a 47-bp deletion when CCCTT sites were separated by 42 bp. Unlike yTop1-initiated large deletions, the vTop1-mediated 47-bp deletion did not require NHEJ, consistent with a model in which re-ligation of enzyme-associated double-strand breaks is catalyzed by vTop1.</p></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"137 ","pages":"Article 103664"},"PeriodicalIF":3.8,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140055003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dominant roles of BRCA1 in cellular tolerance to a chain-terminating nucleoside analog, alovudine","authors":"Md Bayejid Hosen ,&nbsp;Ryotaro Kawasumi ,&nbsp;Kouji Hirota","doi":"10.1016/j.dnarep.2024.103668","DOIUrl":"10.1016/j.dnarep.2024.103668","url":null,"abstract":"<div><p>Alovudine is a chain-terminating nucleoside analog (CTNA) that is frequently used as an antiviral and anticancer agent. Generally, CTNAs inhibit DNA replication after their incorporation into nascent DNA during DNA synthesis by suppressing subsequent polymerization, which restricts the proliferation of viruses and cancer cells. Alovudine is a thymidine analog used as an antiviral drug. However, the mechanisms underlying the removal of alovudine and DNA damage tolerance pathways involved in cellular resistance to alovudine remain unclear. Here, we explored the DNA damage tolerance pathways responsible for cellular tolerance to alovudine and found that BRCA1-deficient cells exhibited the highest sensitivity to alovudine. Moreover, alovudine interfered with DNA replication in two distinct mechanisms: first: alovudine incorporated at the end of nascent DNA interfered with subsequent DNA synthesis; second: DNA replication stalled on the alovudine-incorporated template strand. Additionally, BRCA1 facilitated the removal of the incorporated alovudine from nascent DNA, and BRCA1-mediated homologous recombination (HR) contributed to the progressive replication on the alovudine-incorporated template. Thus, we have elucidated the previously unappreciated mechanism of alovudine-mediated inhibition of DNA replication and the role of BRCA1 in cellular tolerance to alovudine.</p></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"137 ","pages":"Article 103668"},"PeriodicalIF":3.8,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140054883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA repair-related heritable photosensitivity syndromes: Mutation landscape in a multiethnic cohort of 17 multigenerational families with high degree of consanguinity","authors":"Amir Hozhabrpour ,&nbsp;Marzieh Mojbafan ,&nbsp;Fahimeh Palizban ,&nbsp;Fatemeh vahidnezhad ,&nbsp;Saeed Talebi ,&nbsp;Maliheh Amani ,&nbsp;Masoud Garshasbi ,&nbsp;Anoosh Naghavi ,&nbsp;Raziyeh Khalesi ,&nbsp;Parvin Mansouri ,&nbsp;Soheila Sotoudeh ,&nbsp;Hamidreza Mahmoudi ,&nbsp;Aida Varghaei ,&nbsp;Maryam Daneshpazhooh ,&nbsp;Fatemeh Karimi ,&nbsp;Sirous Zeinali ,&nbsp;Elnaz Kalamati ,&nbsp;Jouni Uitto ,&nbsp;Leila Youssefian ,&nbsp;Hassan Vahidnezhad","doi":"10.1016/j.dnarep.2024.103633","DOIUrl":"https://doi.org/10.1016/j.dnarep.2024.103633","url":null,"abstract":"<div><p>Inherited photosensitivity syndromes are a heterogeneous group of genetic skin disorders with tremendous phenotypic variability, characterized by photosensitivity and defective DNA repair, especially nucleotide excision repair. A cohort of 17 Iranian families with heritable photosensitivity syndromes was evaluated to identify their genetic defect. The patients' DNA was analyzed with either whole-exome sequencing or RNA sequencing (RNA-Seq). The interpretations of the genomic results were guided by genome-wide homozygosity mapping. Haplotype analysis was performed for cases with recurrent mutations. RNA-Seq, in addition to mutation detection, was also utilized to confirm the pathogenicity. Thirteen sequence variants, including six previously unreported pathogenic variants, were disclosed in 17 Iranian families, with <em>XPC</em> as the most common mutated gene in 10 families (59%). In one patient, RNA-Seq, as a first-tier diagnostic approach, revealed a non-canonical homozygous germline variant: <em>XPC</em>:c.413–9 T &gt; A. The Sashimi plot showed skipping of exon 4 with dramatic XPC down-expression. Haplotype analysis of <em>XPC</em>:c.2251–1 G&gt;C and <em>XPC</em>:1243 C&gt;T in four families showed common haplotypes of 1.7 Mb and 2.6 Mb, respectively, denoting a founder effect. Lastly, two extremely rare cases were presented in this report: a homozygous <em>UVSSA</em>:c .1990 C&gt;T was disclosed, and <em>ERCC2</em>-related cerebro-oculo-facio-skeletal (COFS) syndrome with an early childhood death. A direct comparison of our data with the results of previously reported cohorts demonstrates the international mutation landscape of DNA repair-related photosensitivity disorders, although population-specific differences were observed.</p></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"136 ","pages":"Article 103633"},"PeriodicalIF":3.8,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139992922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A-T neurodegeneration and DNA damage-induced transcriptional stress","authors":"Tanya T. Paull,&nbsp;Phillip R. Woolley","doi":"10.1016/j.dnarep.2024.103647","DOIUrl":"10.1016/j.dnarep.2024.103647","url":null,"abstract":"<div><p>Loss of the ATM protein kinase in humans results in Ataxia-telangiectasia, a disorder characterized by childhood-onset neurodegeneration of the cerebellum as well as cancer predisposition and immunodeficiency. Although many aspects of ATM function are well-understood, the mechanistic basis of the progressive cerebellar ataxia that occurs in patients is not. Here we review recent progress related to the role of ATM in neurons and the cerebellum that comes from many sources: animal models, post-mortem brain tissue samples, and human neurons in culture. These observations have revealed new insights into the consequences of ATM loss on DNA damage, gene expression, and immune signaling in the brain. Many results point to the importance of reactive oxygen species as well as single-strand DNA breaks in the progression of molecular events leading to neuronal dysfunction. In addition, innate immunity signaling pathways appear to play a critical role in ATM functions in microglia, responding to various forms of nucleic acid sensors and regulating survival of neurons and other cell types. Overall, the results lead to an updated view of transcriptional stress and DNA damage resulting from ATM loss that results in changes in gene expression as well as neuroinflammation that contribute to the cerebellar neurodegeneration observed in patients.</p></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"135 ","pages":"Article 103647"},"PeriodicalIF":3.8,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139819352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of ATM-dependent long non-coding RNAs induced in response to DNA damage","authors":"Marta Podralska ,&nbsp;Marcin Piotr Sajek ,&nbsp;Antonina Bielicka ,&nbsp;Magdalena Żurawek ,&nbsp;Iwona Ziółkowska-Suchanek ,&nbsp;Katarzyna Iżykowska ,&nbsp;Tomasz Kolenda ,&nbsp;Marta Kazimierska ,&nbsp;Marta Elżbieta Kasprzyk ,&nbsp;Weronika Sura ,&nbsp;Barbara Pietrucha ,&nbsp;Bożena Cukrowska ,&nbsp;Natalia Rozwadowska ,&nbsp;Agnieszka Dzikiewicz- Krawczyk","doi":"10.1016/j.dnarep.2024.103648","DOIUrl":"10.1016/j.dnarep.2024.103648","url":null,"abstract":"<div><p>DNA damage response (DDR) is a complex process, essential for cell survival. Especially deleterious type of DNA damage are DNA double-strand breaks (DSB), which can lead to genomic instability and malignant transformation if not repaired correctly. The central player in DSB detection and repair is the ATM kinase which orchestrates the action of several downstream factors. Recent studies have suggested that long non-coding RNAs (lncRNAs) are involved in DDR. Here, we aimed to identify lncRNAs induced upon DNA damage in an ATM-dependent manner. DNA damage was induced by ionizing radiation (IR) in immortalized lymphoblastoid cell lines derived from 4 patients with ataxia-telangiectasia (AT) and 4 healthy donors. RNA-seq revealed 10 lncRNAs significantly induced 1 h after IR in healthy donors, whereas none in AT patients. 149 lncRNAs were induced 8 h after IR in the control group, while only three in AT patients. Among IR-induced mRNAs, we found several genes with well-known functions in DDR. Gene Set Enrichment Analysis and Gene Ontology revealed delayed induction of key DDR pathways in AT patients compared to controls. The induction and dynamics of selected 9 lncRNAs were confirmed by RT-qPCR. Moreover, using a specific ATM inhibitor we proved that the induction of those lncRNAs is dependent on ATM. Some of the detected lncRNA genes are localized next to protein-coding genes involved in DDR. We observed that induction of lncRNAs after IR preceded changes in expression of adjacent genes. This indicates that IR-induced lncRNAs may regulate the transcription of nearby genes. Subcellular fractionation into chromatin, nuclear, and cytoplasmic fractions revealed that the majority of studied lncRNAs are localized in chromatin. In summary, our study revealed several lncRNAs induced by IR in an ATM-dependent manner. Their genomic co-localization and co-expression with genes involved in DDR suggest that those lncRNAs may be important players in cellular response to DNA damage.</p></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"135 ","pages":"Article 103648"},"PeriodicalIF":3.8,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139827865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNF4 prevents genomic instability caused by chronic DNA under-replication","authors":"Marissa K. Oram ,&nbsp;Ryan M. Baxley ,&nbsp;Emily M. Simon ,&nbsp;Kevin Lin ,&nbsp;Ya-Chu Chang ,&nbsp;Liangjun Wang ,&nbsp;Chad L. Myers ,&nbsp;Anja-Katrin Bielinsky","doi":"10.1016/j.dnarep.2024.103646","DOIUrl":"10.1016/j.dnarep.2024.103646","url":null,"abstract":"<div><p>Eukaryotic genome stability is maintained by a complex and diverse set of molecular processes. One class of enzymes that promotes proper DNA repair, replication and cell cycle progression comprises small ubiquitin-like modifier (SUMO)-targeted E3 ligases, or STUbLs. Previously, we reported a role for the budding yeast STUbL synthetically lethal with <em>sgs1</em> (Slx) 5/8 in preventing G₂/M-phase arrest in a minichromosome maintenance protein 10 (Mcm10)-deficient model of replication stress. Here, we extend these studies to human cells, examining the requirement for the human STUbL RING finger protein 4 (RNF4) in <em>MCM10</em> mutant cancer cells. We find that MCM10 and RNF4 independently promote origin firing but regulate DNA synthesis epistatically and, unlike in yeast, the negative genetic interaction between <em>RNF4</em> and <em>MCM10</em> causes cells to accumulate in G₁-phase. When MCM10 is deficient, RNF4 prevents excessive DNA under-replication at hard-to-replicate regions that results in large DNA copy number alterations and severely reduced viability. Overall, our findings highlight that STUbLs participate in species-specific mechanisms to maintain genome stability, and that human RNF4 is required for origin activation in the presence of chronic replication stress.</p></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"135 ","pages":"Article 103646"},"PeriodicalIF":3.8,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1568786424000223/pdfft?md5=840a8eb7861dd76a0526afd8e8da8b68&pid=1-s2.0-S1568786424000223-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA polymerase λ Loop1 variant yields unexpected gain-of-function capabilities in nonhomologous end-joining","authors":"Andrea M. Kaminski ,&nbsp;Kishore K. Chiruvella ,&nbsp;Dale A. Ramsden ,&nbsp;Katarzyna Bebenek ,&nbsp;Thomas A. Kunkel ,&nbsp;Lars C. Pedersen","doi":"10.1016/j.dnarep.2024.103645","DOIUrl":"10.1016/j.dnarep.2024.103645","url":null,"abstract":"<div><p>DNA polymerases lambda (Polλ) and mu (Polμ) are X-Family polymerases that participate in DNA double-strand break (DSB) repair by the nonhomologous end-joining pathway (NHEJ). Both polymerases direct synthesis from one DSB end, using template derived from a second DSB end. In this way, they promote the NHEJ ligation step and minimize the sequence loss normally associated with this pathway. The two polymerases differ in cognate substrate, as Polλ is preferred when synthesis must be primed from a base-paired DSB end, while Polμ is required when synthesis must be primed from an unpaired DSB end. We generated a Polλ variant (Polλ^KGET) that retained canonical Polλ activity on a paired end—albeit with reduced incorporation fidelity. We recently discovered that the variant had unexpectedly acquired the activity previously unique to Polμ—synthesis from an unpaired primer terminus. Though the sidechains of the Loop1 region make no contact with the DNA substrate, Polλ^KGET Loop1 amino acid sequence is surprisingly essential for its unique activity during NHEJ. Taken together, these results underscore that the Loop1 region plays distinct roles in different Family X polymerases.</p></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"136 ","pages":"Article 103645"},"PeriodicalIF":3.8,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1568786424000211/pdfft?md5=0b4d32848371b45daa42695817419cb2&pid=1-s2.0-S1568786424000211-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139661270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variants in the first methionine of RAD51C are homologous recombination proficient due to an alternative start site","authors":"Hayley L. Rein ,&nbsp;Kara A. Bernstein","doi":"10.1016/j.dnarep.2024.103644","DOIUrl":"10.1016/j.dnarep.2024.103644","url":null,"abstract":"<div><p>In the 20+ years since the discovery of RAD51C, scientists have been perplexed as to how missense variants in this tumor suppressor gene impacts its function and pathogenicity. With a strong connection to breast and ovarian cancer, classifying these variants as pathogenic or benign aids in the diagnosis and treatment of patients with RAD51C variants. In particular, variants at translational starts sites are disruptive as they prevent protein expression. These variants are often classified as pathogenic, unless an alternative translational start is shown to produce a functional isoform to rescue protein expression. In this study, we utilized the ribosome profiling database GWIPS-VIZ to identify two active translational start sites in human RAD51C at methionine one and methionine ten. This second translational start at methionine ten is both conserved in 97 % of mammals and is the sole translational start in 80 % of mammals. Missense variants at either methionine have been identified in 47 individuals, preventing expression from one of these two start sites. Therefore, we stably expressed both wildtype isoforms, as well as the RAD51C M1 and M10 variants in a <em>RAD51C</em> CRISPR/Cas9 knockout U2OS cell and compared their homologous recombination function. Surprisingly, we find that expression of human RAD51C from either start site can equivalently rescue homologous recombination of <em>RAD51C</em> CRISPR/Cas9 knockout U2OS cells through a sister chromatid recombination assay. Similarly, each of our <em>RAD51C</em> CRISPR/Cas9 KO cells stably complemented with RAD51C missense variants at either M1 or M10 are homologous recombination proficient. Together, our data demonstrate that RAD51C has two translational start sites and that variants in either methionine result in homologous recombination proficiency. With this critical discovery, individuals with variants at M1 will be more accurately informed of their cancer risk upon reclassification of these variants.</p></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"135 ","pages":"Article 103644"},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139661480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglial inflammation in genome instability: A neurodegenerative perspective","authors":"Nina L. Maliar ,&nbsp;Emily J. Talbot ,&nbsp;Abigail R. Edwards ,&nbsp;Svetlana V. Khoronenkova","doi":"10.1016/j.dnarep.2024.103634","DOIUrl":"10.1016/j.dnarep.2024.103634","url":null,"abstract":"<div><p>The maintenance of genome stability is crucial for cell homeostasis and tissue integrity. Numerous human neuropathologies display chronic inflammation in the central nervous system, set against a backdrop of genome instability, implying a close interplay between the DNA damage and immune responses in the context of neurological disease. Dissecting the molecular mechanisms of this crosstalk is essential for holistic understanding of neuroinflammatory pathways in genome instability disorders. Non-neuronal cell types, specifically microglia, are major drivers of neuroinflammation in the central nervous system with neuro-protective and -toxic capabilities. Here, we discuss how persistent DNA damage affects microglial homeostasis, zooming in on the cytosolic DNA sensing cGAS-STING pathway and the downstream inflammatory response, which can drive neurotoxic outcomes in the context of genome instability.</p></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"135 ","pages":"Article 103634"},"PeriodicalIF":3.8,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1568786424000107/pdfft?md5=ee2eb4fcd9d8c407669b6e8f72591602&pid=1-s2.0-S1568786424000107-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139555880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}