PXD041742

PXD041742 is an original dataset announced via ProteomeXchange.

Title	Dynamics of de novo heterochromatin assembly and disassembly at replication forks ensures fork stability
Description	Chromatin is dynamically reorganized when DNA replication forks are challenged. However, the process of epigenetic reorganization and its implication for fork stability is poorly understood. Here, we discover a checkpoint regulated cascade of chromatin signaling that activates 5 the histone methyltransferase EHMT2/G9a to catalyze heterochromatin assembly at stressed replication forks. Using biochemical and single molecule chromatin fiber approaches, we show that G9a together with SUV39h1 induces chromatin compaction by accumulating the repressive modifications, H3K9me1/me2/me3, in the vicinity of stressed replication forks. This closed conformation is also favored by the G9a-dependent exclusion of the H3K9-demethylase 10 JMJD1A/KDM3A, which facilitates heterochromatin disassembly upon fork restart. Untimely heterochromatin disassembly from stressed forks by KDM3A enables PRIMPOL access, triggering ssDNA gap formation and sensitizing cells towards chemotherapeutic drugs. These findings may help explaining chemotherapy resistance and poor prognosis observed in cancer patients displaying elevated level of G9a/H3K9me3.
HostingRepository	PRIDE
AnnounceDate	2023-05-12
AnnouncementXML	Submission_2023-05-12_06:07:09.207.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JeroenDemmers
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-23 00:34:38	ID requested
⏵ 1	2023-05-12 06:07:09	announced

Dataset with its publication pending

submitter keyword: G9a, SILAC,replication fork, DNA replication

JeroenDemmers
contact affiliation	Proteomics center, Erasmus MC
contact email	j.demmers@erasmusmc.nl
lab head
JeroenDemmers
contact affiliation	Proteomics Center, Erasmus University Medical Center, Rotterdam, The Netherlands
contact email	j.demmers@erasmusmc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041742
     1. Label: PRIDE project
     2. Name: Dynamics of de novo heterochromatin assembly and disassembly at replication forks ensures fork stability