来自微核的粉碎染色体的线粒组
Yu-Fen Lin1, Qing Hu1, Alice Mazzagatti1
1Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nature
|May 10, 2023
概括
在细胞分裂过程中,CIP2A-TOPBP1复合体的切除会阻止非中心DNA片段的聚合. 这种聚类机制解释了染色体的不同模式, 这是一个在癌症中产生复杂基因组重组的过程.
科学领域:
- 遗传学
- 细胞生物学
- 基因组学
背景情况:
- 复杂的基因组重组,包括染色体,由微核中的染色体粉碎产生.
- 在线粒分裂过程中从破碎的染色体中继承的非中心片段仍然不太清楚.
研究的目的:
- 研究在线粒分裂过程中非中心片段遗传的机制.
- 阐明CIP2A-TOPBP1复合体在染色体的作用.
- 在癌症中描述平衡染色体的基因组后果.
主要方法:
- 通过活细胞成像追踪微核染色体.
- 对CIP2A-TOPBP1复合物的功能性失活.
- 分析泛癌基因组以确定重组模式.
主要成果:
- 一个子细胞的不对称继承过程中,非中心的片段聚集在一起.
- CIP2A-TOPBP1复合物调解了与DNA损伤的过早关联,促进了片段的聚合.
- CIP2A-TOPBP1的无活化导致分散的碎片,随机分区和细胞质DNA的积累.
- 线性聚类可以使非中心碎片重新组合成平衡的重排,这与正规的染色异.
- 在不同癌症类型中,平衡染色体的特征是复制数中性重排.
结论:
- 微核中的粉碎染色体的空间聚类是驱动独特染色体形的关键机制.
- CIP2A-TOPBP1复合体在协调这种集群过程中发挥着至关重要的作用.
- 平衡的染色体有助于获得癌症驱动事件.
相关概念视频
Attachment of Sister Chromatids
3.3K
As cells progress into mitosis, the nuclear envelope breaks down, and the condensed chromosomes are exposed to the array of bipolar microtubules of the mitotic spindle. The kinetochore, a large, disc-shaped protein complex, is present at the centromere region of the sister chromatids and acts as a binding site for the microtubules. Usually, the plus-end of a single microtubule is embedded within the kinetochore. However, some kinetochores first establish lateral contact with the side-wall...
3.3K
Separation of Sister Chromatids
3.7K
At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
At the onset of anaphase, separase, a proteolytic enzyme, is...
3.7K
Forces Acting on Chromosomes
3.4K
During mitosis, chromosome movements occur through the interplay of multiple piconewton level forces. In prometaphase, these forces help in chromosome assembly or congression at the equatorial plane, eventually leading to their alignment at the metaphase plate. The forces acting on the chromosomes are space and time-dependent; therefore, they vary with the position of the chromosomes as the cell progresses through mitosis.
Microtubules and motor proteins exert two types of forces on...
Microtubules and motor proteins exert two types of forces on...
3.4K
Polytene Chromosomes
10.1K
Polytene chromosomes are giant interphase chromosomes with several DNA strands placed side by side. They were discovered in the year 1881 by Balbiani in salivary glands, intestine, muscles, malpighian tubules, and hypoderm of larvae Chironomus plumosus. Hence, these are also called "Salivary gland chromosomes." These are found in insects of the order Diptera and Collembola; in certain organs of mammals; and synergids, antipodes of flowering plants. Polytene chromosomes are also...
10.1K
Spindle Assembly
3.7K
Spindle assembly occurs through three, often coexisting, pathways – the centrosome-mediated pathway, the chromatin-mediated pathway, and the microtubule-mediated pathway – collectively contributing to form a robust spindle apparatus.
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a...
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a...
3.7K
Meiosis II
45.9K
Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for meiosis II are similar to mitosis, except that meiosis II occurs in haploid cells, whereas mitosis occurs in diploid cells.
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
45.9K


