Behavior of dicentric chromosomes in budding yeast.
Behavior of dicentric chromosomes in budding yeast.
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芽殖酵母双着丝粒染色体的行为。
DOI：
10.1371/journal.pgen.1009442
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发表时间：
2021-03
期刊：
影响因子：
4.5
通讯作者：
Bloom K
中科院分区：
文献类型：
--
作者：
Cook D;Long S;Stanton J;Cusick P;Lawrimore C;Yeh E;Grant S;Bloom K
当双着丝粒染色体（一条染色体上的两个着丝粒）经历有丝分裂时，两个着丝粒附着在相对的纺锤体极体上，DNA双链断裂就会在体内发生。DSB的修复由于出现的单着丝粒衍生染色体的范围而产生表型多样性。为了探讨是否DSB可能被差异修复作为其在染色体中的空间位置的函数，我们已经研究了单着丝粒衍生染色体的结构，从细胞包含一套双着丝粒染色体，其中两个着丝粒之间的距离范围从6.5 kb到57.7 kb。鉴定了两类主要的修复产物，基于同源性的（同源重组（HR）和单链退火（SSA））和末端连接（非同源性（NHEJ）和微同源性介导的（MMEJ））。修复产物的分布随着两个着丝粒之间的距离而变化。对双链断裂修复（Rad52）、DNA连接酶（Lif1）和S期检查点（Mrc1）的遗传依赖性表明，与臂相比，着丝粒周围染色质中DNA断裂的修复途径选择不同。染色体生物学中的一个挑战是将线性代码与细胞核内的空间组织和染色体动力学相结合。细胞核中功能的主要细分是核仁，即核糖体RNA合成的场所。我们报告说，着丝粒周围的着丝粒DNA是另一个区域的限制生物化学。我们已经发现，位于染色体的着丝粒周围区域内的两个着丝粒之间的染色体断裂通过不依赖于序列同源性（MMEJ或NHEJ）的途径修复。着丝粒间隔> 20 kb的双着丝粒染色体中的染色体断裂通过主要依赖于序列同源性的途径修复（HR，SSA）。在pericentromere与武器中的断裂的修复是差异依赖于Rad52，Lif1，和Mrc1，进一步表明对DNA修复途径的空间控制。
DNA double-strand breaks arise in vivo when a dicentric chromosome (two centromeres on one chromosome) goes through mitosis with the two centromeres attached to opposite spindle pole bodies. Repair of the DSBs generates phenotypic diversity due to the range of monocentric derivative chromosomes that arise. To explore whether DSBs may be differentially repaired as a function of their spatial position in the chromosome, we have examined the structure of monocentric derivative chromosomes from cells containing a suite of dicentric chromosomes in which the distance between the two centromeres ranges from 6.5 kb to 57.7 kb. Two major classes of repair products, homology-based (homologous recombination (HR) and single-strand annealing (SSA)) and end-joining (non-homologous (NHEJ) and micro-homology mediated (MMEJ)) were identified. The distribution of repair products varies as a function of distance between the two centromeres. Genetic dependencies on double strand break repair (Rad52), DNA ligase (Lif1), and S phase checkpoint (Mrc1) are indicative of distinct repair pathway choices for DNA breaks in the pericentromeric chromatin versus the arms. A challenge in chromosome biology is to integrate the linear code with spatial organization and chromosome dynamics within the nucleus. The major sub-division of function in the nucleus is the nucleolus, the site of ribosomal RNA synthesis. We report that the pericentromere DNA surrounding the centromere is another region of confined biochemistry. We have found that chromosome breaks between two centromeres that both lie within the pericentromeric region of the chromosomes are repaired via pathways that do not rely on sequence homology (MMEJ or NHEJ). Chromosome breaks in dicentric chromosomes whose centromeres are separated by > 20 kb are repaired via pathways that rely mainly on sequence homology (HR, SSA). The repair of breaks in the pericentromere versus breaks in the arms are differentially dependent on Rad52, Lif1, and Mrc1, further indicative of spatial control over DNA repair pathways.
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DOI：
10.1126/science.aan6490
发表时间：
2018-01-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kabeche L;Nguyen HD;Buisson R;Zou L
通讯作者：
Zou L
影响因子：
8.8
作者：
Harding SM;Boiarsky JA;Greenberg RA
通讯作者：
Greenberg RA
影响因子：
64.8
作者：
Katou, Y;Kanoh, Y;Shirahige, K
通讯作者：
Shirahige, K
影响因子：
16
作者：
Defossez, PA;Prusty, R;Guarente, L
通讯作者：
Guarente, L
影响因子：
11.4
作者：
JAGER, D;PHILIPPSEN, P
通讯作者：
PHILIPPSEN, P