Purpose

Environmental pollutants are known to induce DNA breaks, leading to genomic instability. Here, we propose a novel mechanism for the genotoxic effects exerted by environmentally exposed endocrine-disrupting chemicals (EDCs).

Methods

Bibliographic research and presentation of the analysis.

Discussion

In mammals, nucleotide excision repair, base excision repair, homologous recombination and non-homologous end-joining pathways are some of the major DNA repair pathways. p300 along with CREB-binding protein (CBP) contributes to chromatin remodeling, DNA damage response and repair of both single- and double-stranded DNA breaks. In addition to its role in DNA repair, CBP/p300 also acts as a coactivator to interact with the estrogen receptor and androgen receptor during its estrogen- and androgen-dependent transactivation, respectively. Since activated estrogen receptors (ERs) seize p300 from the repressed genes and redistribute it to the enhancer genes to activate transcription, the cellular functioning may be based on a balance between these pathways and any disturbance in one may alter the other, leading to undesirable physiological effects.

Conclusion

In conclusion, CBP/p300 is important for DNA repair and nuclear hormone receptor transactivation. Activated hormone receptors can sequester p300 to regulate the hormonal effects. Hence, we believe that activation of ERs by EDCs results in sequestration of CBP/p300 for ER transactivation and transcription initiation of its target genes, leading to a competition for CBP/P300, resulting in the deregulation of all other pathways involving p300/CBP.

中文翻译：

---

破坏内分泌的化学物质可能通过雌激素受体介导的CBP / p300乙酰化酶捕获而使DNA修复失调。

目的

已知环境污染物会诱导DNA断裂，从而导致基因组不稳定。在这里，我们提出了一种由环境暴露的内分泌干扰化学物质（EDC）产生的遗传毒性作用的新机制。

方法

书目研究和分析介绍。

讨论区

在哺乳动物中，核苷酸切除修复，碱基切除修复，同源重组和非同源末端连接途径是一些主要的DNA修复途径。p300与CREB结合蛋白（CBP）共同促进了染色质重塑，DNA损伤反应以及单链和双链DNA断裂的修复。除了其在DNA修复中的作用外，CBP / p300在其依赖雌激素和雄激素的反式激活过程中，还充当了与雌激素受体和雄激素受体相互作用的共激活剂。由于活化的雌激素受体（ERs）从阻抑的基因中夺取p300并将其重新分布至增强子基因以激活转录，因此细胞功能可能基于这些途径之间的平衡，而任何一种途径的紊乱都可能改变另一种途径，从而导致不良的生理反应效果。

结论

总之，CBP / p300对于DNA修复和核激素受体反式激活非常重要。激活的激素受体可以隔离p300以调节激素作用。因此，我们认为EDCs激活ER会导致CBP / p300的螯合，从而实现ER的反式激活和其靶基因的转录起始，从而导致对CBP / P300的竞争，从而导致涉及p300 / CBP的所有其他途径的失控。