Jalan Manisha, Olsen Kyrie S, Powell Simon N
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Cancers (Basel). 2019 Jul 23;11(7):1038. doi: 10.3390/cancers11071038.
The maintenance of genome integrity is critical for cell survival. Homologous recombination (HR) is considered the major error-free repair pathway in combatting endogenously generated double-stranded lesions in DNA. Nevertheless, a number of alternative repair pathways have been described as protectors of genome stability, especially in HR-deficient cells. One of the factors that appears to have a role in many of these pathways is human RAD52, a DNA repair protein that was previously considered to be dispensable due to a lack of an observable phenotype in knock-out mice. In later studies, RAD52 deficiency has been shown to be synthetically lethal with defects in BRCA genes, making RAD52 an attractive therapeutic target, particularly in the context of BRCA-deficient tumors.
基因组完整性的维持对细胞存活至关重要。同源重组(HR)被认为是对抗内源性产生的DNA双链损伤的主要无差错修复途径。然而,一些替代修复途径已被描述为基因组稳定性的保护者,尤其是在HR缺陷细胞中。在许多这些途径中似乎起作用的因素之一是人类RAD52,一种DNA修复蛋白,由于在基因敲除小鼠中缺乏可观察到的表型,以前被认为是可有可无的。在后来的研究中,RAD52缺陷已被证明与BRCA基因缺陷具有合成致死性,这使得RAD52成为一个有吸引力的治疗靶点,特别是在BRCA缺陷肿瘤的背景下。