Topoisomerase I is an evolutionarily conserved key regulator for satellite DNA transcription

Zhen Teng, Lu Yang, Qian Zhang, Yujue Chen, Xianfeng Wang, Yiran Zheng, Aiguo Tian, Di Tian, Zhen Lin, Wu-Min Deng and Hong Liu ()
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Zhen Teng: Tulane University School of Medicine
Lu Yang: Tulane University School of Medicine
Qian Zhang: Tulane University School of Medicine
Yujue Chen: Tulane University School of Medicine
Xianfeng Wang: Tulane University School of Medicine
Yiran Zheng: Tulane University School of Medicine
Aiguo Tian: Tulane University School of Medicine
Di Tian: Tulane University School of Medicine
Zhen Lin: Tulane University School of Medicine
Wu-Min Deng: Tulane University School of Medicine
Hong Liu: Tulane University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract RNA Polymerase (RNAP) II transcription on non-coding repetitive satellite DNAs plays an important role in chromosome segregation, but a little is known about the regulation of satellite transcription. We here show that Topoisomerase I (TopI), not TopII, promotes the transcription of α-satellite DNAs, the main type of satellite DNAs on human centromeres. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation. Interestingly, in response to DNA double-stranded breaks (DSBs), α-satellite transcription is dramatically stimulated in a DNA damage checkpoint-independent but TopI-dependent manner, and these DSB-induced α-satellite RNAs form into strong speckles in the nucleus. Remarkably, TopI-dependent satellite transcription also exists in mouse 3T3 and Drosophila S2 cells and in Drosophila larval imaginal wing discs and tumor tissues. Altogether, our findings herein reveal an evolutionally conserved mechanism with TopI as a key player for the regulation of satellite transcription at both cellular and animal levels.

Date: 2024
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DOI: 10.1038/s41467-024-49567-5

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