PXD041562-1

PXD041562 is an original dataset announced via ProteomeXchange.

Title	Transmembrane nuclease NUMEN/ENDOD1 regulates DNA repair pathway choice at the nuclear periphery
Description	Proper repair of DNA damage lesions is essential to maintaining genome integrity and preventing the development of human diseases including cancer. Increasing evidence suggests the importance of the nuclear envelope in the spatial regulation of DNA repair, although the mechanisms of such regulatory processes remain poorly defined. Through a genome-wide synthetic viability screen for PARP inhibitor (PARPi) resistance using an inducible CRISPR/Cas9 platform and BRCA1-deficient breast cancer cells, we identified a transmembrane nuclease (renamed NUMEN) that could facilitate compartmentalized and NHEJ-dependent repair of DNA double-strand breaks at the nuclear periphery. Collectively, our data demonstrate that NUMEN generates short 5’ overhangs through its endonuclease and 3’-5’ exonuclease activities, promotes the repair of DNA lesions including heterochromatic LAD breaks as well as deprotected telomeres, and functions as a downstream effector of DNA-PKcs. These findings underline NUMEN’s role as a key player in DNA repair pathway choice and genome stability maintenance and have implications for ongoing research into the development and treatment of genome instability disorders.
HostingRepository	PRIDE
AnnounceDate	2023-04-19
AnnouncementXML	Submission_2023-04-19_08:29:24.805.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	TianyuGe
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	biotinylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-16 06:09:10	ID requested
⏵ 1	2023-04-19 08:29:25	announced

Dataset with its publication pending

submitter keyword: NUMEN, nuclear membrane, double-strand break, DNA repair, dual-specificity nuclease, NHEJ,PARPi resistance

ZhouSongyang
contact affiliation	MOE Key Laboratory of Gene Function and Regulation and Guangzhou Key Laboratory of Healthy Aging Research, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China
contact email	songyanz@mail.sysu.edu.cn
lab head
TianyuGe
contact affiliation	MOE Key Laboratory of Gene Function and Regulation and Guangzhou Key Laboratory of Healthy Aging Research, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China
contact email	getiany@mail2.sysu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041562
     1. Label: PRIDE project
     2. Name: Transmembrane nuclease NUMEN/ENDOD1 regulates DNA repair pathway choice at the nuclear periphery