Proteomics

Dataset Information

0

RAD51AP1 regulates ALT-HDR through chromatin-directed homeostasis of TERRA


ABSTRACT: Alternative lengthening of telomeres (ALT) is a homology-directed repair (HDR) mechanism of telomere elongation that controls proliferation in subsets of highly aggressive cancer. Recent studies have revealed that TERRA (telomere repeat-containing RNA) acts to initiate ALT-associated HDR (ALT-HDR). Here we report that RAD51AP1, a crucial ALT factor, interacts with TERRA and utilizes it to generate D- and R- loop HR intermediates. We also show that RAD51AP1 binds to and may generate and potentially stabilize TERRA-containing R-loops as RAD51AP1 depletion reduces R-loop formation at telomere DNA breaks. Proteomic analyses uncover a new role for RAD51AP1 mediated TERRA R-loop homeostasis in a mechanism of chromatin-directed suppression of TERRA and prevention of transcription-replication collisions during ALT-HDR. Intriguingly, we find that both TERRA binding and this non-canonical function of RAD51AP1 require its intrinsic SUMO-SIM regulatory axis. These findings provide new insights into the multi-contextual functions of RAD51AP1 within the ALT mechanism and regulation of TERRA.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Alexey Nesvizhskii  

LAB HEAD: Roderick J O'Sullivan

PROVIDER: PXD035943 | Pride | 2024-01-26

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
MSB20134Sample3Band_01.mzXML Mzxml
MSB20134Sample3Band_02.mzXML Mzxml
MSB20134Sample3Band_03.mzXML Mzxml
MSB20134Sample3Band_04.mzXML Mzxml
MSB20134Sample3Band_05.mzXML Mzxml
Items per page:
1 - 5 of 133
altmetric image

Publications


Alternative lengthening of telomeres (ALT) is a homology-directed repair (HDR) mechanism of telomere elongation that controls proliferation in subsets of aggressive cancer. Recent studies have revealed that telomere repeat-containing RNA (TERRA) promotes ALT-associated HDR (ALT-HDR). Here, we report that RAD51AP1, a crucial ALT factor, interacts with TERRA and utilizes it to generate D- and R-loop HR intermediates. We also show that RAD51AP1 binds to and might stabilize TERRA-containing R-loops  ...[more]

Similar Datasets

2023-12-13 | GSE219212 | GEO
2023-12-13 | GSE219146 | GEO
2023-12-13 | GSE240690 | GEO
2020-01-31 | PXD016772 | Pride
2022-09-28 | PXD028882 | Pride
2020-10-12 | PXD020243 | Pride
2021-04-21 | MSV000087276 | MassIVE
2022-03-04 | PXD032093 |
2023-01-18 | PXD034986 | Pride
2022-07-01 | GSE134135 | GEO