线粒体转录终止因子蛋白家族研究进展

线粒体转录终止因子蛋白的作用是与线粒体DNA的特异位点结合,导致线粒体基因转录停止。近年来,随着人们对线粒体基因转录机制和人线粒体疾病的深入研究,线粒体转录终止因子的功能开始受到人们的关注。本文介绍了线粒体转录终止因子及其家族成员的研究进展和有待解决的一些问题。     

Zinc finger protein 668 interacts with Tip60 to promote H2AX acetylation after DNA damage

Many tumor suppressors play an important role in the DNA damage pathway. Zinc finger protein 668 (ZNF668) has recently been identified as one of the potential tumor suppressors in breast cancer, but its function in DNA damage response is unknown. Herein, we report that ZNF668 is a regulator of DNA repair. ZNF668 knockdown impairs cell survival after DNA damage without affecting the ATM/ATR DNA-damage signaling cascade. However, recruitment of repair proteins to DNA lesions is decreased. In response to IR, ZNF668 knockdown reduces Tip60-H2AX interaction and impairs IR-induced histone H2AX hyperacetylation, thus impairing chromatin relaxation. Impaired chromatin relaxation causes decreased recruitment of repair proteins to DNA lesions, defective homologous recombination (HR) repair and impaired cell survival after IR. In addition, ZNF668 knockdown decreased RPA phosphorylation and its recruitment to DNA damage foci in response to UV. In both IR and UV damage responses, chromatin relaxation counteracted the impaired loading of repair proteins and DNA repair defects in ZNF668-deficient U2OS cells, indicating that impeded chromatin accessibility at sites of DNA breaks caused the DNA repair defects observed in the absence of ZNF668. Our findings suggest that ZNF668 is a key molecule that links chromatin relaxation with DNA damage response in DNA repair control.     

线粒体DNA及其应用

线粒体DNA是在真核生物中普遍存在的一种核外遗传物质,具有分子小、结构简单、进化速度快、母性遗传、无组织特异性等特点。本综述了线粒体DNA在人类遗传疾病、动植物的亲缘关系、种群分化、群体多样性及植物细胞质雄性不育等研究领域中的应用情况。