PXD017838-1

PXD017838 is an original dataset announced via ProteomeXchange.

Title	A DOT1B/RNaseH2 protein complex is involved in R-loop processing, genomic integrity and antigenic variation in Trypanosoma brucei
Description	The parasite Trypanosoma brucei periodically changes the expression of its protective variant surface glycoproteins (VSGs) to evade the host’s immune system in a process known as antigenic variation. One route to change VSG expression is by transcriptional activation of a previously silent VSG expression site (ES), a subtelomeric region containing the VSG genes. Homologous recombination of a different VSG from a large reservoir into the active ES represents another route. The conserved histone methyltransferase DOT1B is involved in transcriptional silencing of inactive ES and influences ES switching kinetics. The molecular machinery that enables DOT1B to execute these regulatory functions remains elusive, however. To better understand DOT1B-mediated regulatory processes, we purified DOT1B-associated proteins using complementary biochemical approaches. We identified several novel DOT1B interactors. One of these was the trimeric Ribonuclease H2 complex, previously shown to resolve RNA-DNA hybrids, maintain genome integrity, and play a role in antigenic variation. Our study revealed that DOT1B depletion results in an increase in RNA-DNA hybrids, accumulation of DNA damage and recombination-based ES switching events. Surprisingly, the observed VSG deregulation was similar to Ribonuclease H2 mutants. We here propose that the epigenetic regulator DOT1B forms a complex with RNase H2 that acts in resolving R-loops to ensure genome integrity and contribute to the tightly regulated process of antigenic variation.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_10:37:18.523.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	F Butter
SpeciesList	scientific name: Trypanosoma brucei; NCBI TaxID: 5691;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-03 00:48:59	ID requested
⏵ 1	2024-10-07 10:37:18	announced

Dataset with its publication pending

submitter keyword: trypanosomes,LC MS-MS

Falk Butter
contact affiliation	Institute of Molecular Biology Ackermannweg 4 55128 Mainz
contact email	f.butter@imb.de
lab head
F Butter
contact affiliation	Quantitative Proteomics Institute of Molecular Biology (IMB)
contact email	f.butter@imb-mainz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD017838
     1. Label: PRIDE project
     2. Name: A DOT1B/RNaseH2 protein complex is involved in R-loop processing, genomic integrity and antigenic variation in Trypanosoma brucei