SPSB1

The salivary gland (SGS) is a kind of organ vulnerable to ionizing radiation. Radiotherapy is an important treatment for head and neck tumors, but in the process of radiotherapy, tumor cells will be injured by radiation to a certain extent. Infrared-induced DNA double-strand break (IR-DSBs) is one of the most serious DNA damage. DNA repair proteins such as Nymegan rupture syndrome protein 1 (NBS1) play a key role in the identification and repair of DNA damage. but the interaction between SSB1 and NBS1 has not been elucidated. In this study, we irradiated rat submandibular gland (SMG) cells, which were either infected with a rAdE5-SSB1-1p2-shRNA recombinant adenovirus to silence SSB or a control virus, to explore the effect of IR on the expression NBS1 in the absence of SSB. Our results showed that the SSB1 mRNA transcripts and protein expression of SSB1 and NBS1 initially increased and decreased later with increased doses. The relative expression reached the highest levels when the SMG cells were irradiated with 2Gy of IR. Silencing the SSB1 gene suppressed the expression of both SSB1 and NBS1 regardless of irradiation. The expression of NBS1 decreased when the SSB1 gene was silenced. We concluded that IR affected the expression of both SSB1 and NBS1 and there is a synergistic effect on IR-induced NBS1 suppression and DSBs repair in SMG cells. These observations shed light on further investigation and elucidation of IR-caused DNA repair mechanisms.

The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions^1,2. Here, we identify SOSS-INTAC as a stable association of the genome stability regulator Sensor of Single-stranded DNA (ssDNA) (SOSS)³ and the transcription regulator Integrator-PP2A (INTAC)^4-6. Via SSB1-mediated ssDNA recognition, SOSS-INTAC stimulates promoter-proximal termination of transcription and attenuates paused Pol II-associated R-loops to prevent R-loop-induced genome instability. SOSS-INTAC-dependent attenuation of R-loops is enhanced by SSB1's ability to form liquid-like condensates. Deletion of, or introduction of cancer-associated mutations within its intrinsically disordered region (IDR), leads to pervasive accumulation of R-loops, highlighting a genome surveillance function of SOSS-INTAC that enables timely termination of transcription at promoters to constrain R-loop accumulation to ensure genome stability.

In Saccharomyces cerevisiae, the J-protein Zuo1 and the nonconventional Hsp70 homologue Ssz1 stimulate the ATPase activity of the chaperone proteins Ssb1 and Ssb2 (Ssb1/2), which are associated with the ribosomes. The phosphorylation of sucrose nonfermenting 1 (Snf1) on Thr210 (Snf1-Thr210-Pi) is required for glucose repression. The Ssb1/2 and 14-3-3 proteins Bmh1 and Bmh2 appear to be responsible for Snf1-Thr210-Pi and glucose repression. Here, we investigated the role of Zuo1 in glucose repression. The zuo1∆ strain as well as the ssb1∆ssb2∆ strain exhibited a glucose-specific growth defect during logarithmic growth on glucose. Many of the respiratory chain genes examined were statistically significantly upregulated, but less than 2-fold, in the zuo1∆ strain as well as in the ssb1∆ssb2∆ strain on glucose. In addition, excessive Snf1-Thr210-Pi was observed in the zuo1∆ strain as well as in the ssb1∆ssb2∆ strain in the presence of glucose. The mRNA levels of SSB1/2 and BMH1 were statistically significantly reduced by approximately 0.5- to 0.8-fold relative to the wild-type level in the zuo1∆ strain on glucose. These results suggest that Zuo1 is responsible for glucose repression, possibly by increasing the mRNA levels of SSB1/2 and BMH1 during growth on glucose.