Proteomics

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PSer2-RNAPII interaction partners in MEF cells (label free)

ABSTRACT: Deregulation of RNA Polymerase II (RNAPII) by oncogenic signaling leads to collisions of RNAPII with DNA synthesis machinery (transcription-replication conflicts, TRCs). TRCs can result in DNA damage and underlie genomic instability in tumor cells. Here we provide evidence that elongating RNAPII promotes activation of the ATM kinase at TRCs to drive DNA repair. We show the ATPase Wrnip1 that binds and protects stalled replication forks, associates with RNAPII and limits ATM activation. Wrnip1 binding to elongating RNAPII requires catalytic activity of the ubiquitin ligase Huwe1. Mutation of Huwe1 promotes the transfer of Wrnip1 onto replisome and induces TRCs stimulating ATM activation on RNAPII. This mechanism is evoked early upon replicative stress to induce Wrnip1 translocation and ATM signaling at TRCs. Thus, although primarily considered as genotoxic events, TRCs can provide a mechanism to maintain genome stability under replicative stress.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Epithelial Cell, Cell Culture

SUBMITTER: Elias Einig  

LAB HEAD: Nikita Popov

PROVIDER: PXD037680 | Pride | 2023-07-31

REPOSITORIES: Pride

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20201230_CO_0956ElEi_WT_IgG_1.raw Raw
20201230_CO_0956ElEi_WT_IgG_2.raw Raw
20201230_CO_0956ElEi_WT_IgG_3.raw Raw
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Publications

RNAPII-dependent ATM signaling at collisions with replication forks.

Einig Elias E   Jin Chao C   Andrioletti Valentina V   Macek Boris B   Popov Nikita N  

Nature communications 20230824 1

Deregulation of RNA Polymerase II (RNAPII) by oncogenic signaling leads to collisions of RNAPII with DNA synthesis machinery (transcription-replication conflicts, TRCs). TRCs can result in DNA damage and are thought to underlie genomic instability in tumor cells. Here we provide evidence that elongating RNAPII nucleates activation of the ATM kinase at TRCs to stimulate DNA repair. We show the ATPase WRNIP1 associates with RNAPII and limits ATM activation during unperturbed cell cycle. WRNIP1 bin  ...[more]

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