Genomics

Dataset Information

0

Survival of cells with deregulated MYC requires UVSSA-dependent regulation of RNAPII dynamics


ABSTRACT: Cancer cells develop strong genetic dependencies enabling survival under oncogenic stress. MYC is a key oncogene activated across most cancers, and identifying associated synthetic lethality can provide important clues about its activity and potential therapeutic strategies. Based on previously conducted genome-wide screenings we identified UVSSA, a gene involved in transcription-coupled repair whose knockdown decreased cell viability when combined with MYC activation. Synthetic lethal interactions between MYC expression and UVSSA loss correlated with ATM/CHK2 activation, suggesting increased genome instability. We show that although the synthetic lethal interaction was diminished by attenuating RNA polymerase II (RNAPII) activity, it becomes independent of UV-induced damage repair, suggesting that UVSSA has a critical function in regulating transcription in the absence of exogenous DNA damage. Supporting this hypothesis, RNAPII-ChIP-seq revealed that MYC-dependent increase in RNAPII promoter occupancy, as well as RNAPII stalling, is reduced or abrogated by UVSSA knockdown, suggesting that UVSSA negatively regulates MYC-dependent transcription. Taken together, our data shows that the UVSSA complex is required to limit MYC-dependent transcription stress and to maintain cell survival. While the role of UVSSA in regulating RNAPII dynamics has only been documented thus far in the context of UV-induced DNA damage repair, we propose that its activity is also required to cope with transcription stress induced by oncogene activation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE121960 | GEO | 2020/10/28

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2020-04-13 | GSE132840 | GEO
2021-02-28 | PXD016198 | Pride
2023-07-24 | PXD037854 | Pride
2021-02-15 | PXD023242 | Pride
2024-09-02 | GSE266085 | GEO
2024-09-02 | GSE266083 | GEO
2021-01-15 | GSE140930 | GEO
2020-04-14 | PXD013572 | Pride
2014-03-31 | E-GEOD-50947 | biostudies-arrayexpress
2022-10-27 | PXD036674 | Pride