Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Nature ; 587(7832): 126-132, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32879494

RESUMO

Chromosomal instability in cancer consists of dynamic changes to the number and structure of chromosomes1,2. The resulting diversity in somatic copy number alterations (SCNAs) may provide the variation necessary for tumour evolution1,3,4. Here we use multi-sample phasing and SCNA analysis of 1,421 samples from 394 tumours across 22 tumour types to show that continuous chromosomal instability results in pervasive SCNA heterogeneity. Parallel evolutionary events, which cause disruption in the same genes (such as BCL9, MCL1, ARNT (also known as HIF1B), TERT and MYC) within separate subclones, were present in 37% of tumours. Most recurrent losses probably occurred before whole-genome doubling, that was found as a clonal event in 49% of tumours. However, loss of heterozygosity at the human leukocyte antigen (HLA) locus and loss of chromosome 8p to a single haploid copy recurred at substantial subclonal frequencies, even in tumours with whole-genome doubling, indicating ongoing karyotype remodelling. Focal amplifications that affected chromosomes 1q21 (which encompasses BCL9, MCL1 and ARNT), 5p15.33 (TERT), 11q13.3 (CCND1), 19q12 (CCNE1) and 8q24.1 (MYC) were frequently subclonal yet appeared to be clonal within single samples. Analysis of an independent series of 1,024 metastatic samples revealed that 13 focal SCNAs were enriched in metastatic samples, including gains in chromosome 8q24.1 (encompassing MYC) in clear cell renal cell carcinoma and chromosome 11q13.3 (encompassing CCND1) in HER2+ breast cancer. Chromosomal instability may enable the continuous selection of SCNAs, which are established as ordered events that often occur in parallel, throughout tumour evolution.


Assuntos
Instabilidade Cromossômica/genética , Evolução Molecular , Cariótipo , Metástase Neoplásica/genética , Neoplasias/genética , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 8/genética , Células Clonais/metabolismo , Células Clonais/patologia , Ciclina E/genética , Variações do Número de Cópias de DNA/genética , Feminino , Humanos , Perda de Heterozigosidade/genética , Masculino , Mutagênese , Metástase Neoplásica/patologia , Neoplasias/patologia , Proteínas Oncogênicas/genética
2.
Nucleic Acids Res ; 50(18): 10487-10502, 2022 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-36200807

RESUMO

Proteins with RNA-binding activity are increasingly being implicated in DNA damage responses (DDR). Additionally, DNA:RNA-hybrids are rapidly generated around DNA double-strand breaks (DSBs), and are essential for effective repair. Here, using a meta-analysis of proteomic data, we identify novel DNA repair proteins and characterise a novel role for DDX17 in DNA repair. We found DDX17 to be required for both cell survival and DNA repair in response to numerous agents that induce DSBs. Analysis of DSB repair factor recruitment to damage sites suggested a role for DDX17 early in the DSB ubiquitin cascade. Genome-wide mapping of R-loops revealed that while DDX17 promotes the formation of DNA:RNA-hybrids around DSB sites, this role is specific to loci that have low levels of pre-existing hybrids. We propose that DDX17 facilitates DSB repair at loci that are inefficient at forming DNA:RNA-hybrids by catalysing the formation of DSB-induced hybrids, thereby allowing propagation of the damage response.


Assuntos
RNA Helicases DEAD-box/metabolismo , Reparo do DNA , Linhagem Celular Tumoral , Quebras de DNA de Cadeia Dupla , Células HeLa , Humanos , Proteômica , Ubiquitinas/genética
3.
Nucleic Acids Res ; 42(5): 3298-313, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24335285

RESUMO

A key player in translation initiation is eIF4E, the mRNA 5' cap-binding protein. 4E-Transporter (4E-T) is a recently characterized eIF4E-binding protein, which regulates specific mRNAs in several developmental model systems. Here, we first investigated the role of its enrichment in P-bodies and eIF4E-binding in translational regulation in mammalian cells. Identification of the conserved C-terminal sequences that target 4E-T to P-bodies was enabled by comparison of vertebrate proteins with homologues in Drosophila (Cup and CG32016) and Caenorhabditis elegans by sequence and cellular distribution. In tether function assays, 4E-T represses bound mRNA translation, in a manner independent of these localization sequences, or of endogenous P-bodies. Quantitative polymerase chain reaction and northern blot analysis verified that bound mRNA remained intact and polyadenylated. Ectopic 4E-T reduces translation globally in a manner dependent on eIF4E binding its consensus Y30X4L site. In contrast, tethered 4E-T continued to repress translation when eIF4E-binding was prevented by mutagenesis of YX4L, and modestly enhanced the decay of bound mRNA, compared with wild-type 4E-T, mediated by increased binding of CNOT1/7 deadenylase subunits. As depleting 4E-T from HeLa cells increased steady-state translation, in part due to relief of microRNA-mediated silencing, this work demonstrates the conserved yet unconventional mechanism of 4E-T silencing of particular subsets of mRNAs.


Assuntos
MicroRNAs/metabolismo , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Biossíntese de Proteínas , Interferência de RNA , Proteínas de Drosophila/análise , Proteínas de Drosophila/química , Fator de Iniciação 4E em Eucariotos/metabolismo , Células HeLa , Humanos , Proteínas de Transporte Nucleocitoplasmático/análise , Proteínas de Transporte Nucleocitoplasmático/química , Estabilidade de RNA , RNA Mensageiro/metabolismo , RNA Viral/metabolismo , Proteínas Repressoras/análise , Proteínas Repressoras/química
4.
Biochem Soc Trans ; 42(1): 166-72, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24450646

RESUMO

The eIF4A (eukaryotic initiation factor 4A) proteins belong to the extensive DEAD-box RNA helicase family, the members of which are involved in many aspects of RNA metabolism by virtue of their RNA-binding capacity and ATPase activity. Three eIF4A proteins have been characterized in vertebrates: eIF4A1 and eIF4A2 are cytoplasmic, whereas eIF4A3 is nuclear-localized. Although highly similar, they have been shown to possess rather diverse roles in the mRNA lifecycle. Their specific and diverse functions are often regulated and dictated by interacting partner proteins. The key differences between eIF4A family members are discussed in the present review.


Assuntos
Fator de Iniciação 4A em Eucariotos/fisiologia , Sequência de Aminoácidos , Animais , Sequência Conservada , Fator de Iniciação 4A em Eucariotos/química , Regulação da Expressão Gênica , Humanos , Anotação de Sequência Molecular , Dados de Sequência Molecular , Filogenia
5.
Nat Commun ; 15(1): 6039, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39019871

RESUMO

During each cell cycle, the process of DNA replication timing is tightly regulated to ensure the accurate duplication of the genome. The extent and significance of alterations in this process during malignant transformation have not been extensively explored. Here, we assess the impact of altered replication timing (ART) on cancer evolution by analysing replication-timing sequencing of cancer and normal cell lines and 952 whole-genome sequenced lung and breast tumours. We find that 6%-18% of the cancer genome exhibits ART, with regions with a change from early to late replication displaying an increased mutation rate and distinct mutational signatures. Whereas regions changing from late to early replication contain genes with increased expression and present a preponderance of APOBEC3-mediated mutation clusters and associated driver mutations. We demonstrate that ART occurs relatively early during cancer evolution and that ART may have a stronger correlation with mutation acquisition than alterations in chromatin structure.


Assuntos
Neoplasias da Mama , Período de Replicação do DNA , Neoplasias Pulmonares , Mutação , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Linhagem Celular Tumoral , Desaminases APOBEC/genética , Desaminases APOBEC/metabolismo , Taxa de Mutação , Replicação do DNA/genética , Genoma Humano
6.
Nat Genet ; 56(1): 60-73, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38049664

RESUMO

In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Regulação para Cima/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Citidina Desaminase/genética , Antígenos de Histocompatibilidade Menor/genética , Antígenos de Histocompatibilidade Menor/metabolismo
7.
Blood ; 117(23): 6277-86, 2011 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-21478426

RESUMO

Faithful repair of DNA lesions is a crucial task that dividing cells must actively perform to maintain genome integrity. Strikingly, nucleotide excision repair (NER), the most versatile DNA repair system, is specifically down-regulated in terminally differentiated cells. This prompted us to examine whether NER attenuation might be a common feature of all G0-arrested cells, and in particular of those that retain the capacity to reenter cell cycle and might thus convert unrepaired DNA lesions into mutations, a prerequisite for malignant transformation. Here we report that quiescent primary human B lymphocytes down-regulate NER at the global genome level while maintaining proficient repair of constitutively expressed genes. Quiescent B cells exposed to an environment that causes both DNA damage and proliferation accumulate point mutations in silent and inducible genes crucial for cell replication and differentiation, such as BCL6 and Cyclin D2. Similar to differentiated cells, NER attenuation in quiescent cells is associated with incomplete phosphorylation of the ubiquitin activating enzyme Ube1, which is required for proficient NER. Our data establish a mechanistic link between NER attenuation during quiescence and cell mutagenesis and also support the concept that oncogenic events targeting cell cycle- or activation-induced genes might initiate genomic instability and lymphomagenesis.


Assuntos
Linfócitos B/metabolismo , Dano ao DNA/genética , Reparo do DNA/genética , Regulação para Baixo/genética , Genoma Humano , Mutagênese , Mutação , Fase de Repouso do Ciclo Celular/genética , Linfócitos B/citologia , Ciclina D2/genética , Ciclina D2/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Instabilidade Genômica , Humanos , Proteínas Proto-Oncogênicas c-bcl-6 , Enzimas Ativadoras de Ubiquitina
8.
Open Life Sci ; 18(1): 20220750, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37941789

RESUMO

Malignant melanoma (MM) frequently occurs in the skin or mucosa, whereas malignant melanoma of unknown primary (MUP) is diagnosed in patients with lymph nodes or visceral organs as the site of origin, where it is challenging to detect the primary lesion by comprehensive examination. MUP is possibly related to the spontaneous regression of the primary lesion. In addition, primary hepatic melanoma (PHM) usually refers to the primary MM occurring in the liver, with no typical primary lesions and no manifestations of tumor metastasis. A 61-year-old male patient with liver as the site of origin was diagnosed with MM by Melan-A, HMB-45, and S-100 immunohistochemistry staining of liver biopsy tissue. Based on a comprehensive examination, no basis was found for melanoma in sites such as the skin, mucosa, five sense organs, brain, digestive tract, respiratory tract, or genitalia, and the patient was subsequently diagnosed with MUP. MMs require a comprehensive inspection, beginning with the liver, to search for the primary lesion; if the primary lesion is not found, the possibility of PHM or MUP should be considered.

9.
Am J Cancer Res ; 12(6): 2659-2672, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35812043

RESUMO

Microscopic vascular invasion (MVI) is a strong risk factor associated with tumor recurrence and poor overall survival (OS) among hepatocellular carcinoma (HCC) patients after resection. Two types of MVI are identified: portal vein and capsular vein invasion. However, little is known about the impact of different types of MVI on HCC recurrence. The present study aimed to compare HCC recurrence and OS between the portal vein and capsule vein MVI. Patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A HCC who underwent primary resection between January 2001 and June 2016 were consecutively recruited. Factors that influenced OS and recurrence-free survival (RFS) were analyzed using Cox proportional hazards models. Of the 857 eligible patients, 327 (38.2%) had MVI, and 530 (61.8%) were without MVI. Of the 327 patients with MVI, 85 (26.0%) were with portal vein, 178 (54.4%) with capsular vein, and 64 (19.6%) with both-MVI type. Patients with both-MVI type suffered from a higher proportion of BCLC stage A (P < 0.001), capsular invasion (P = 0.002), and satellite nodules (P < 0.001). Both-MVI type is an independent risk factor for HCC recurrence (hazard ratio [HR]: 1.69; 95% CI, 1.22-2.36, P = 0.002) and mortality (HR: 2.29; 95% CI, 1.59-3.29, P < 0.001) compared with non-MVI. We further found that both-MVI type was significantly associated with a higher risk of extrahepatic recurrence (EHR) (HR: 8.74; 95% CI, 2.38-32.03, P = 0.001). Among HCC patients after curative resection, concurrent portal and capsular MVI is a risk factor for HCC recurrence, especially for EHR, in comparison with non-MVI or only portal or capsular MVI alone.

10.
Wellcome Open Res ; 6: 9, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34095506

RESUMO

The ongoing pandemic of SARS-CoV-2 calls for rapid and cost-effective methods to accurately identify infected individuals. The vast majority of patient samples is assessed for viral RNA presence by RT-qPCR. Our biomedical research institute, in collaboration between partner hospitals and an accredited clinical diagnostic laboratory, established a diagnostic testing pipeline that has reported on more than 252,000 RT-qPCR results since its commencement at the beginning of April 2020. However, due to ongoing demand and competition for critical resources, alternative testing strategies were sought. In this work, we present a clinically-validated procedure for high-throughput SARS-CoV-2 detection by RT-LAMP in 25 minutes that is robust, reliable, repeatable, sensitive, specific, and inexpensive.

11.
Cancer Discov ; 11(10): 2456-2473, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33947663

RESUMO

APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when APOBEC3 expression is induced during cancer development remains to be defined. Here we show that specific APOBEC3 genes are upregulated in breast ductal carcinoma in situ, and in preinvasive lung cancer lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx preinvasive to invasive non-small cell lung cancer (NSCLC) lesions. We find that APOBEC3B exacerbates DNA replication stress and chromosomal instability through incomplete replication of genomic DNA, manifested by accumulation of mitotic ultrafine bridges and 53BP1 nuclear bodies in the G1 phase of the cell cycle. Analysis of TRACERx NSCLC clinical samples and mouse lung cancer models revealed APOBEC3B expression driving replication stress and chromosome missegregation. We propose that APOBEC3 is functionally implicated in the onset of chromosomal instability and somatic mutational heterogeneity in preinvasive disease, providing fuel for selection early in cancer evolution. SIGNIFICANCE: This study reveals the dynamics and drivers of APOBEC3 gene expression in preinvasive disease and the exacerbation of cellular diversity by APOBEC3B through DNA replication stress to promote chromosomal instability early in cancer evolution.This article is highlighted in the In This Issue feature, p. 2355.


Assuntos
Desaminases APOBEC/genética , Neoplasias da Mama/genética , Carcinoma Ductal/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Animais , Linhagem Celular Tumoral , Instabilidade Cromossômica , Replicação do DNA , Feminino , Humanos , Camundongos
13.
Genome Biol ; 20(1): 262, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791371

RESUMO

BACKGROUND: Regulation of the mRNA life cycle is central to gene expression control and determination of cell fate. miRNAs represent a critical mRNA regulatory mechanism, but despite decades of research, their mode of action is still not fully understood. RESULTS: Here, we show that eIF4A2 is a major effector of the repressive miRNA pathway functioning via the Ccr4-Not complex. We demonstrate that while DDX6 interacts with Ccr4-Not, its effects in the mechanism are not as pronounced. Through its interaction with the Ccr4-Not complex, eIF4A2 represses mRNAs at translation initiation. We show evidence that native eIF4A2 has similar RNA selectivity to chemically inhibited eIF4A1. eIF4A2 exerts its repressive effect by binding purine-rich motifs which are enriched in the 5'UTR of target mRNAs directly upstream of the AUG start codon. CONCLUSIONS: Our data support a model whereby purine motifs towards the 3' end of the 5'UTR are associated with increased ribosome occupancy and possible uORF activation upon eIF4A2 binding.


Assuntos
RNA Helicases DEAD-box/metabolismo , Regulação da Expressão Gênica , MicroRNAs/fisiologia , Receptores CCR4/metabolismo , Fatores de Transcrição/metabolismo , Regiões 5' não Traduzidas , Humanos
14.
Nat Commun ; 9(1): 532, 2018 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-29416038

RESUMO

The error-free and efficient repair of DNA double-stranded breaks (DSBs) is extremely important for cell survival. RNA has been implicated in the resolution of DNA damage but the mechanism remains poorly understood. Here, we show that miRNA biogenesis enzymes, Drosha and Dicer, control the recruitment of repair factors from multiple pathways to sites of damage. Depletion of Drosha significantly reduces DNA repair by both homologous recombination (HR) and non-homologous end joining (NHEJ). Drosha is required within minutes of break induction, suggesting a central and early role for RNA processing in DNA repair. Sequencing of DNA:RNA hybrids reveals RNA invasion around DNA break sites in a Drosha-dependent manner. Removal of the RNA component of these structures results in impaired repair. These results show how RNA can be a direct and critical mediator of DNA damage repair in human cells.


Assuntos
Dano ao DNA , Reparo do DNA , DNA/metabolismo , RNA/metabolismo , Ribonuclease III/metabolismo , Células A549 , Linhagem Celular Tumoral , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , DNA/genética , Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades , Perfilação da Expressão Gênica , Recombinação Homóloga , Humanos , RNA/genética , Interferência de RNA , Ribonuclease III/genética
15.
Cell Death Differ ; 24(11): 1989, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28862702

RESUMO

This corrects the article DOI: 10.1038/cdd.2017.16.

16.
Cell Death Differ ; 24(4): 580-587, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28234355

RESUMO

Many surveillance and repair mechanisms exist to maintain the integrity of our genome. All of the pathways described to date are controlled exclusively by proteins, which through their enzymatic activities identify breaks, propagate the damage signal, recruit further protein factors and ultimately resolve the break with little to no loss of genetic information. RNA is known to have an integral role in many cellular pathways, but, until very recently, was not considered to take part in the DNA repair process. Several reports demonstrated a conserved critical role for RNA-processing enzymes and RNA molecules in DNA repair, but the biogenesis of these damage-related RNAs and their mechanisms of action remain unknown. We will explore how these new findings challenge the idea of proteins being the sole participants in the response to DNA damage and reveal a new and exciting aspect of both DNA repair and RNA biology.


Assuntos
Dano ao DNA , RNA/metabolismo , RNA Helicases DEAD-box/metabolismo , Reparo do DNA , Histonas/metabolismo , Humanos , MicroRNAs/metabolismo , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo
17.
Zhonghua Gan Zang Bing Za Zhi ; 14(11): 832-4, 2006 Nov.
Artigo em Zh | MEDLINE | ID: mdl-17125611

RESUMO

OBJECTIVE: Drug-induced liver damage is a potential complication from using many drugs. The aim of our study was to analyze the etiology and clinical features of drug-induced liver damage, in order to draw more attention to this problem. METHODS: Two hundred and seventy-six cases over a 5-year period in Jiangsu Province Hospital were retrospectively analyzed. RESULTS: A variety of drugs, including traditional Chinese medicines (26.1% of our total cases) and anticancer drugs (17%) caused liver damage. The main clinical manifestations of it were fatigue, nausea, vomiting and jaundice. In 88% of our cases the symptoms were relieved or completely disappeared, but there was still a 5.1% mortality rate. CONCLUSIONS: The clinical features of drug-induced liver damage are of no specificity, and the mortality of it is not low. Liver function should be monitored when suspected drugs are prescribed.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas/classificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Hepática Crônica Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Crônica Induzida por Substâncias e Drogas/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
20.
Cell Cycle ; 10(19): 3300-10, 2011 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-21926477

RESUMO

The Fanconi anaemia (FA) pathway is a DNA-damage inducible pathway critical for genomic stability. FA patients typically display high cancer susceptibility and hypersensitivity to DNA-damaging agents such as cross-linkers and ionizing radiation. A key step in the activation of the FA pathway is monoubiquitination of the FancD2 protein. Here we report that the FA pathway is downregulated by two distinct mechanisms upon differentiation of THP-1 and HL-60 leukaemia cells into macrophages. Firstly, qRT-PCR analysis revealed a transcriptional downregulation of most components of the FA complex, including FancD2. Secondly, DNA damage-induced monoubiquitination of the remaining FancD2 became deficient at various stages of differentiation depending on the type of damage. This was attributed to the differentiation-induced downregulation of Chk1, which phosphorylates FancD2 as a prelude to its ubiquitination. Although Western blotting revealed that levels of FancD2 were greatly reduced in terminally differentiated macrophages and that FancD2 ubiquitination was abolished, double-strand breaks were proficiently repaired, likely through an increase in non-homologous end joining (NHEJ). It has been suggested that the FA pathway promotes repair of double-strand breaks via homologous recombination rather than NHEJ. Its downregulation in macrophages may thus be required to avoid promoting a repair mechanism that is inefficient in post-mitotic cells.


Assuntos
Diferenciação Celular , Regulação para Baixo , Anemia de Fanconi/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Linhagem Celular , Quinase 1 do Ponto de Checagem , Dano ao DNA , Reparo do DNA por Junção de Extremidades , Anemia de Fanconi/patologia , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo , Recombinação Homóloga , Humanos , Fosforilação , Proteínas Quinases/metabolismo , Ubiquitinação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA