PT  - JOURNAL ARTICLE
AU  - Dou Peng
AU  - Li Yiqun
AU  - Xie Wanqiu
AU  - Zhang Xiaoqing
AU  - Zhang Dandan
AU  - Ci Yanpeng
AU  - Zhang Xiaohan
AU  - Qiao Shupei
AU  - Muhammad Luqman Akhtar
AU  - Han Fang
AU  - Yu Li
TI  - C1orf109L promote R-loop accumulation induced DNA damage to inhibit cell growth
AID  - 10.1101/625749
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 625749
4099  - http://biorxiv.org/content/early/2019/05/02/625749.short
4100  - http://biorxiv.org/content/early/2019/05/02/625749.full
AB  - As a function unknown gene, C1orf109 is lower expression in various cells. Here, we reported that C1orf109L, the longest variant of C1orf109, which interacted with R-loop-regulating proteins to trigger R-loop, a three-stranded nucleic acid structure frequently mediated genome instability, accumulation. C1orf109L induce chronic DNA damage to promote P21 upregulation and strongly inhibits cell growth in vitro and in vivo by arresting the cell cycle in the G2 phase. With camptothecin (CPT), an R-loop activator, treatment, C1orf109L further triggers R-loop accumulation-induced DNA damage and promotes cell death by activating cell-death pathway. Furthermore, CPT treatment increases C1orf109L ubiquitination and turnover, which inhibits cell death and promotes the G0/G1 phase of the cell cycle. Therefore, our data illustrated the mechanisms underlying C1orf109L-related cell growth inhibition and provide feasibility and limitations for C1orf109L as a potential target for cancer therapy.