Zhang Qi, Hao Rongjiao, Chen Hongxia, Zhou Gangqiao
Graduate Collaborative Training Base of Academy of Military Sciences, Hengyang Medical School, University of South China, Hengyang City, Hunan Province, 421001, P.R. China.
School of Life Sciences, Hebei University, Baoding City, Hebei Province, 071002, P.R. China.
Cell Death Discov. 2023 Aug 28;9(1):319. doi: 10.1038/s41420-023-01619-3.
Human single-stranded DNA-binding protein homologs hSSB1 (SOSSB1) and hSSB2 (SOSSB2) make a vital impact on maintaining genome stability as the B subunits of the sensor of single-stranded DNA complex (SOSS). However, whether and how SOSSB1 and SOSSB2 modulate mutual expression is unclear. This study, demonstrated that the depletion of SOSSB1 in cells enhances the stability of the SOSSB2 protein, and conversely, SOSSB2 depletion enhances the stability of the SOSSB1 protein. The levels of SOSSB1 and SOSSB2 proteins are mutually regulated through their competitive binding with SOSSA which associates with the highly conservative OB-fold domain in SOSSB1 and SOSSB2. The destabilized SOSSB1 and SOSSB2 proteins can be degraded via the proteasome pathway. Additionally, the simultaneous loss of SOSSB1 and SOSSB2 aggravates homologous recombination (HR)-mediated DNA repair defects, enhances cellular radiosensitivity and promotes cell apoptosis. In conclusion, in this study, we showed that SOSSB1 and SOSSB2 positively regulate HR repair and the interaction between SOSSA and SOSSB1 or SOSSB2 prevents the degradation of SOSSB1 and SOSSB2 proteins via the proteasome pathway.
人类单链DNA结合蛋白同源物hSSB1（SOSSB1）和hSSB2（SOSSB2）作为单链DNA复合物传感器（SOSS）的B亚基，对维持基因组稳定性具有至关重要的影响。然而，SOSSB1和SOSSB2是否以及如何调节彼此的表达尚不清楚。本研究表明，细胞中SOSSB1的缺失会增强SOSSB2蛋白的稳定性，反之，SOSSB2的缺失会增强SOSSB1蛋白的稳定性。SOSSB1和SOSSB2蛋白的水平通过它们与SOSSA的竞争性结合而相互调节，SOSSA与SOSSB1和SOSSB2中高度保守的OB折叠结构域相关联。不稳定的SOSSB1和SOSSB2蛋白可通过蛋白酶体途径降解。此外，SOSSB1和SOSSB2的同时缺失会加剧同源重组（HR）介导的DNA修复缺陷，增强细胞放射敏感性并促进细胞凋亡。总之，在本研究中，我们表明SOSSB1和SOSSB2正向调节HR修复，并且SOSSA与SOSSB1或SOSSB2之间的相互作用可防止SOSSB1和SOSSB2蛋白通过蛋白酶体途径降解。
