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1.
The formation of healthy gametes depends on programmed DNA double-strand breaks (DSBs), which are each repaired as a crossover (CO) or non-crossover (NCO) from a homologous template. Although most of these DSBs are repaired without giving COs, little is known about the genetic requirements of NCO-specific recombination. We show that Fml1, the Fanconi anemia complementation group M (FANCM)-ortholog of Schizosaccharomyces pombe, directs the formation of NCOs during meiosis in competition with the Mus81-dependent pro-CO pathway. We also define the Rad51/Dmc1-mediator Swi5-Sfr1 as a major determinant in biasing the recombination process in favor of Mus81, to ensure the appropriate amount of COs to guide meiotic chromosome segregation. The conservation of these proteins from yeast to humans suggests that this interplay may be a general feature of meiotic recombination.  相似文献   

2.
The number of meiotic crossovers (COs) is tightly regulated within a narrow range, despite a large excess of molecular precursors. The factors that limit COs remain largely unknown. Here, using a genetic screen in Arabidopsis thaliana, we identified the highly conserved FANCM helicase, which is required for genome stability in humans and yeasts, as a major factor limiting meiotic CO formation. The fancm mutant has a threefold-increased CO frequency as compared to the wild type. These extra COs arise not from the pathway that accounts for most of the COs in wild type, but from an alternate, normally minor pathway. Thus, FANCM is a key factor imposing an upper limit on the number of meiotic COs, and its manipulation holds much promise for plant breeding.  相似文献   

3.
Sister-chromatid cohesion, established during replication by the protein complex cohesin, is essential for both chromosome segregation and double-strand break (DSB) repair. Normally, cohesion formation is strictly limited to the S phase of the cell cycle, but DSBs can trigger cohesion also after DNA replication has been completed. The function of this damage-induced cohesion remains unknown. In this investigation, we show that damage-induced cohesion is essential for repair in postreplicative cells in yeast. Furthermore, it is established genome-wide after induction of a single DSB, and it is controlled by the DNA damage response and cohesin-regulating factors. We thus define a cohesion establishment pathway that is independent of DNA duplication and acts together with cohesion formed during replication in sister chromatid-based DSB repair.  相似文献   

4.
Mechanism of RAD51-dependent DNA interstrand cross-link repair   总被引:2,自引:0,他引:2  
DNA interstrand cross-links (ICLs) are toxic DNA lesions whose repair in S phase of eukaryotic cells is incompletely understood. In Xenopus egg extracts, ICL repair is initiated when two replication forks converge on the lesion. Dual incisions then create a DNA double-strand break (DSB) in one sister chromatid, whereas lesion bypass restores the other sister. We report that the broken sister chromatid is repaired via RAD51-dependent strand invasion into the regenerated sister. Recombination acts downstream of FANCI-FANCD2, yet RAD51 binds ICL-stalled replication forks independently of FANCI-FANCD2 and before DSB formation. Our results elucidate the functional link between the Fanconi anemia pathway and the recombination machinery during ICL repair. In addition, they demonstrate the complete repair of a DSB via homologous recombination in vitro.  相似文献   

5.
Meiosis requires that each chromosome find its homologous partner and undergo at least one crossover. X-Y chromosome segregation hinges on efficient crossing-over in a very small region of homology, the pseudoautosomal region (PAR). We find that mouse PAR DNA occupies unusually long chromosome axes, potentially as shorter chromatin loops, predicted to promote double-strand break (DSB) formation. Most PARs show delayed appearance of RAD51/DMC1 foci, which mark DSB ends, and all PARs undergo delayed DSB-mediated homologous pairing. Analysis of Spo11β isoform-specific transgenic mice revealed that late RAD51/DMC1 foci in the PAR are genetically distinct from both early PAR foci and global foci and that late PAR foci promote efficient X-Y pairing, recombination, and male fertility. Our findings uncover specific mechanisms that surmount the unique challenges of X-Y recombination.  相似文献   

6.
Faithful chromosome segregation and repair of DNA double-strand breaks (DSBs) require cohesin, the protein complex that mediates sister-chromatid cohesion. Cohesion between sister chromatids is thought to be generated only during ongoing DNA replication by an obligate coupling between cohesion establishment factors such as Eco1 (Ctf7) and the replisome. Using budding yeast, we challenge this model by showing that cohesion is generated by an Eco1-dependent but replication-independent mechanism in response to DSBs in G(2)/M. Furthermore, our studies reveal that Eco1 has two functions: a cohesive activity and a conserved acetyltransferase activity, which triggers the generation of cohesion in response to the DSB and the DNA damage checkpoint. Finally, the DSB-induced cohesion is not limited to broken chromosomes but occurs also on unbroken chromosomes, suggesting that the DNA damage checkpoint through Eco1 provides genome-wide protection of chromosome integrity.  相似文献   

7.
SIRT6 promotes DNA repair under stress by activating PARP1   总被引:2,自引:0,他引:2  
Sirtuin 6 (SIRT6) is a mammalian homolog of the yeast Sir2 deacetylase. Mice deficient for SIRT6 exhibit genome instability. Here, we show that in mammalian cells subjected to oxidative stress SIRT6 is recruited to the sites of DNA double-strand breaks (DSBs) and stimulates DSB repair, through both nonhomologous end joining and homologous recombination. Our results indicate that SIRT6 physically associates with poly[adenosine diphosphate (ADP)-ribose] polymerase 1 (PARP1) and mono-ADP-ribosylates PARP1 on lysine residue 521, thereby stimulating PARP1 poly-ADP-ribosylase activity and enhancing DSB repair under oxidative stress.  相似文献   

8.
Interactions between ends from different DNA double-strand breaks (DSBs) can produce tumorigenic chromosome translocations. Two theories for the juxta-position of DSBs in translocations, the static "contact-first" and the dynamic "breakage-first" theory, differ fundamentally in their requirement for DSB mobility. To determine whether or not DSB-containing chromosome domains are mobile and can interact, we introduced linear tracks of DSBs in nuclei. We observed changes in track morphology within minutes after DSB induction, indicating movement of the domains. In a subpopulation of cells, the domains clustered. Juxtaposition of different DSB-containing chromosome domains through clustering, which was most extensive in G1 phase cells, suggests an adhesion process in which we implicate the Mre11 complex. Our results support the breakage-first theory to explain the origin of chromosomal translocations.  相似文献   

9.
李昕 《油气储运》2013,32(4):343-348
碳捕集与封存作为减少温室气体排放的重要手段成为全球研究热点,管道运输是该技术得以实施的关键环节。当CO2处于超临界或密相状态时,其具有液体的密度、气体的粘性和压缩性,对于管道运输是最有效率的。由于管输CO2的特殊性质,CO2输送管道与碳氢化合物输送管道存在不同;由于海洋环境的复杂性,CO2海上输送管道与陆地输送管道存在不同。系统总结了实现CO2管道输送需要解决的关键技术问题,着重介绍了CO2输送管道流动保障和延性断裂扩展领域的研究进展,指出CCS作为大规模减少温室气体排放的重要选项,开展与之相关的基础研究十分迫切。(图3,参44)  相似文献   

10.
In mammalian cells, repair of DNA double-strand breaks (DSBs) by nonhomologous end-joining (NHEJ) is critical for genome stability. Although the end-bridging and ligation steps of NHEJ have been reconstituted in vitro, little is known about the end-processing reactions that occur before ligation. Recently, functionally homologous end-bridging and ligation activities have been identified in prokarya. Consistent with its homology to polymerases and nucleases, we demonstrate that DNA ligase D from Mycobacterium tuberculosis (Mt-Lig) possesses a unique variety of nucleotidyl transferase activities, including gap-filling polymerase, terminal transferase, and primase, and is also a 3' to 5' exonuclease. These enzyme activities allow the Mt-Ku and Mt-Lig proteins to join incompatible DSB ends in vitro, as well as to reconstitute NHEJ in vivo in yeast. These results demonstrate that prokaryotic Ku and ligase form a bona fide NHEJ system that encodes all the recognition, processing, and ligation activities required for DSB repair.  相似文献   

11.
减少食物浪费是保障粮食安全、缓解全球气候变暖的重要举措。基于中国健康与营养调查(CHNS)和中国食品生命周期评估数据库(CFLCAD),从南北主食差异这一视角出发,基于生命周期理论分析中国居民家庭的食物浪费碳足迹。研究发现,中国居民家庭人均日食物浪费碳足迹为62.255 g CO2eq。相比以小麦为主食的北方家庭(人均食物浪费碳足迹为53.704 g CO2eq/d),以大米为主食的南方家庭有着更高的人均食物浪费碳足迹(69.628 g CO2eq/d)。此外,显著影响家庭食物浪费碳足迹的还有户主年龄、主要女性成员年龄、主要女性成员受教育年限、家庭人口规模与结构、收入水平、储藏条件和膳食知识、家庭类型等变量。  相似文献   

12.
Mutations in the BRCA2 (breast cancer susceptibility gene 2) tumor suppressor lead to chromosomal instability due to defects in the repair of double-strand DNA breaks (DSBs) by homologous recombination, but BRCA2's role in this process has been unclear. Here, we present the 3.1 angstrom crystal structure of a approximately 90-kilodalton BRCA2 domain bound to DSS1, which reveals three oligonucleotide-binding (OB) folds and a helix-turn-helix (HTH) motif. We also (i) demonstrate that this BRCA2 domain binds single-stranded DNA, (ii) present its 3.5 angstrom structure bound to oligo(dT)9, (iii) provide data that implicate the HTH motif in dsDNA binding, and (iv) show that BRCA2 stimulates RAD51-mediated recombination in vitro. These findings establish that BRCA2 functions directly in homologous recombination and provide a structural and biochemical basis for understanding the loss of recombination-mediated DSB repair in BRCA2-associated cancers.  相似文献   

13.
The somatic chromosome number of the cultivated Trifolium hirtum All. (rose clover) is 10. Satellites occur on one pair of the chromosomes. Out of approximately 70 species of this genus for which the chromosome numbers are known, only one other has a chromosome number of 10.  相似文献   

14.
In eukaryotic cells, double-strand breaks (DSBs) in DNA are generally repaired by the pathway of homologous recombination or by DNA nonhomologous end joining (NHEJ). Both pathways have been highly conserved throughout eukaryotic evolution, but no equivalent NHEJ system has been identified in prokaryotes. The NHEJ pathway requires a DNA end-binding component called Ku. We have identified bacterial Ku homologs and show that these proteins retain the biochemical characteristics of the eukaryotic Ku heterodimer. Furthermore, we show that bacterial Ku specifically recruits DNA ligase to DNA ends and stimulates DNA ligation. Loss of these proteins leads to hypersensitivity to ionizing radiation in Bacillus subtilis. These data provide evidence that many bacteria possess a DNA DSB repair apparatus that shares many features with the NHEJ system of eukarya and suggest that this DNA repair pathway arose before the prokaryotic and eukaryotic lineages diverged.  相似文献   

15.
Saturation of the southern ocean CO2 sink due to recent climate change   总被引:2,自引:0,他引:2  
Based on observed atmospheric carbon dioxide (CO2) concentration and an inverse method, we estimate that the Southern Ocean sink of CO2 has weakened between 1981 and 2004 by 0.08 petagrams of carbon per year per decade relative to the trend expected from the large increase in atmospheric CO2. We attribute this weakening to the observed increase in Southern Ocean winds resulting from human activities, which is projected to continue in the future. Consequences include a reduction of the efficiency of the Southern Ocean sink of CO2 in the short term (about 25 years) and possibly a higher level of stabilization of atmospheric CO2 on a multicentury time scale.  相似文献   

16.
各国棉花育种工作都在开展野生二倍体棉种的利用问题。试验用二倍体亚洲棉G。arboreum 2n(2x)=26,染色体组A_2,与野生比克氏棉G. bickii, 2n(2x)=26,染色体组G杂交,获得异源二倍体杂种。因二者亲缘关系最远,杂种高度不育。对A_2×GF_1PMC减数分裂观察,M_2染色体大都不配对,二价体变幅1—6对,并出现三价体,染色体构型为1.64Ⅰ+4.0Ⅱ+0.4Ⅲ。平均交叉频率为1.07个。由于四分体发育不正常,形成畸形败育花粉,导致杂种F_1高度不育。对A_2×G F_1进行染色体加倍,合成异源四倍体,观察F_2PMC减数分裂时,染色体数为52条。MI,大都配对,交叉频率为1.83,大多数为环状二价体。染色体构型为:2.75Ⅰ+24.5Ⅱ+0.25Ⅲ。其中完全配对成26个二价体的细胞数占30%。后期Ⅰ,染色体平均分配,两级各有26条,形成正常的四分体,花粉生活力达89%杂种植株育性恢复,每株结铃平均为33个,每铃种子平均9.1粒,为人工合成异源四倍体新种质  相似文献   

17.
二氧化碳输送管道工程设计的关键问题   总被引:3,自引:0,他引:3  
刘建武 《油气储运》2014,(4):369-373
CO2管道输送是碳捕集、利用和封存(CCUS)技术的重要环节,具有真正意义的长距离、大输量CO2管道在国内尚属空白。结合二氧化碳物性特点和国外二氧化碳输送管道建设经验,对国内二氧化碳输送管道工程设计在气源气体组分要求、输送相态的选择和控制、路由选择、阀室设计原则、地区等级划分、涂层选用、设备材料的密封性能、管材性能以及其他安全措施等方面进行了深入探讨,分别提出了切实可行的建议措施,指出编制适合中国国情的CO2输送管道的设计、建造、运营规范十分迫切。研究内容对于推动我国二氧化碳输送管道工程和CCUS技术的发展具有重要意义。(图1,表1,参7)  相似文献   

18.
Nonhomologous end joining (NHEJ) is a critical DNA double-strand break (DSB) repair pathway required to maintain genome stability. Many prokaryotes possess a minimalist NHEJ apparatus required to repair DSBs during stationary phase, composed of two conserved core proteins, Ku and ligase D (LigD). The crystal structure of Mycobacterium tuberculosis polymerase domain of LigD mediating the synapsis of two noncomplementary DNA ends revealed a variety of interactions, including microhomology base pairing, mismatched and flipped-out bases, and 3' termini forming hairpin-like ends. Biochemical and biophysical studies confirmed that polymerase-induced end synapsis also occurs in solution. We propose that this DNA synaptic structure reflects an intermediate bridging stage of the NHEJ process, before end processing and ligation, with both the polymerase and the DNA sequence playing pivotal roles in determining the sequential order of synapsis and remodeling before end joining.  相似文献   

19.
We used strong-field laser pulses that were tailored with closed-loop optimal control to govern specified chemical dissociation and reactivity channels in a series of organic molecules. Selective cleavage and rearrangement of chemical bonds having dissociation energies up to approximately 100 kilocalories per mole (about 4 electron volts) are reported for polyatomic molecules, including (CH3)2CO (acetone), CH3COCF3 (trifluoroacetone), and C6H5COCH3 (acetophenone). Control over the formation of CH(3)CO from (CH3)2CO, CF3 (or CH3) from CH3COCF3, and C6H5CH3 (toluene) from C6H5COCH3 was observed with high selectivity. Strong-field control appears to have generic applicability for manipulating molecular reactivity because the tailored intense laser fields (about 10(13) watts per square centimeter) can dynamically Stark shift many excited states into resonance, and consequently, the method is not confined by resonant spectral restrictions found in the perturbative (weak-field) regime.  相似文献   

20.
从相态控制角度,以东方1-1气田在海南岛陆上终端排放的CO2为例,开展了CO2长距离管输压力和管径的优化研究,并对管道入口压力、入口温度及环境温度等因素进行敏感性分析。结果表明:管输压力对CO2的输送相态具有重要影响,且很大程度上决定管径和壁厚,进而影响管道经济性;管输压力应保持在CO2临界压力之上,在无保温措施的情况下,CO2始终呈高压密相状态(超临界状态或液态),能保持管道的正常运行;对于东方1-1气田伴生CO2长距离输送方案,推荐管输压力为9MPa或16MPa,管材采用X65钢,不必采取保温措施。(图4,参14)  相似文献   

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