Tacconi Eliana M C, Tarsounas Madalena
Telomere and Genome Stability Group, The CRUK-MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
Chromosoma. 2015 Jun;124(2):119-30. doi: 10.1007/s00412-014-0497-2. Epub 2014 Nov 29.
Telomeres protect the ends of linear chromosomes against loss of genetic information and inappropriate processing as damaged DNA and are therefore crucial to the maintenance of chromosome integrity. In addition to providing a pathway for genome-wide DNA repair, homologous recombination (HR) plays a key role in telomere replication and capping. Consistent with this, the genomic instability characteristic of HR-deficient cells and tumours is driven in part by telomere dysfunction. Here, we discuss the mechanisms by which HR modulates the response to intrinsic cellular challenges that arise during telomere replication, as well as its impact on the assembly of telomere protective structures. How normal and tumour cells differ in their ability to maintain telomeres is deeply relevant to the search for treatments that would selectively eliminate cells whose capacity for HR-mediated repair has been compromised.
端粒保护线性染色体的末端，防止遗传信息丢失以及因DNA受损而出现的不当处理，因此对于维持染色体完整性至关重要。除了为全基因组DNA修复提供一条途径外，同源重组（HR）在端粒复制和加帽过程中也起着关键作用。与此一致的是，HR缺陷型细胞和肿瘤的基因组不稳定特征部分是由端粒功能障碍驱动的。在这里，我们讨论HR调节对端粒复制过程中出现的内在细胞挑战的反应的机制，以及其对端粒保护结构组装的影响。正常细胞和肿瘤细胞在维持端粒能力上的差异与寻找能够选择性消除HR介导修复能力受损细胞的治疗方法密切相关。
