通过TMEJ进行的线粒DNA修复抑制了复制应激诱导的核外重组缺陷的复制
Guojun Ye1,2, Yide He2, Yihui Zhang2,3,4
1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Nature communications
|October 3, 2025
概括
复制应激会导致核膜重组缺陷 (NERD) 在线粒分裂过程中,与DNA损伤有关. 修复这种损坏和理解复制应激敏感的LAD可能会改善核外的完整性.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 遗传学 是一个
背景情况:
- 如果不解决,复制应激 (RS) 可以在线粒分裂期间导致DNA损伤.
- RS与核外 (NE) 动态等线粒体事件之间的相互作用尚未得到充分理解.
研究的目的:
- 为了研究复制应激对核包膜完整性在转化过程中的影响.
- 阐明在复制应激条件下核外缺陷背后的机制.
主要方法:
- 研究了由复制压力引起的核外缺陷.
- 使用目标下切割和标记 (CUT&Tag) 来进行层状相关域 (LAD) 的基因组映射.
- 评估了DNA聚合酶甲基 (Polθ) 中介末端结合 (TMEJ) 在修复线性DNA损伤及其对核膜重组缺陷 (NERD) 的作用.
主要成果:
- 复制应力会导致核外缺陷,特别是核外重组缺陷 (NERD),而不是 de novo 破裂.
- NERD与线粒DNA损伤有关,而TMEJ介导的修复改善了NERD.
- 鉴定了复制应激敏感的LADs (RESSLADs),其中许多位于常见脆弱部位 (CFSs),并将它们的NE相互作用损失与拉敏A/C酸化联系起来.
结论:
- 建立了复制压力和核膜在线粒分裂过程中的脆弱性之间的直接联系.
- 强调了NERD的作用及其与线粒体DNA损伤和修复途径的关联.
- 表明RESSLADs及其与NE的相互作用对复制压力敏感,导致基因组不稳定.
相关概念视频
02:31Homologous Recombination
62.6K
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
62.6K
01:02The DNA Replication Fork
40.4K
An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork. Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication...
40.4K
01:02The DNA Replication Fork
18.1K
18.1K
01:20Mismatch Repair
6.3K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
6.3K
01:36Mismatch Repair
43.5K
Overview
43.5K
02:10Translesion DNA Polymerases
11.0K
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
11.0K