PXD062780

PXD062780 is an original dataset announced via ProteomeXchange.

Title	C8orf33 dictates DNA double-strand break repair choice by modulating KAT8-mediated H4K16 acetylation
Description	DNA double-strand breaks (DSBs) are repaired through distinct pathways, including homologous recombination (HR) and non-homologous end joining (NHEJ). The regulation of repair pathway choice is crucial for maintaining genomic stability and preventing carcinogenesis. Consequently, there is growing interest in elucidating the molecular mechanisms that govern DSB repair pathway selection. Here, we identify chromosome 8 open reading frame 33 (C8orf33) as a novel regulator of DSB repair choice. We show that C8orf33 is a nuclear protein localized predominantly to the nucleolus and is recruited to DSB sites within both the nuclear and nucleolar regions. We demonstrate that C8orf33 promotes the recruitment of 53BP1, thus channeling DSB repair toward NHEJ. In doing so, C8orf33 inhibits DNA end resection and counteracts the recruitment of HR factors, BRCA1 and RAD51, to DSB sites. Mechanistically, chromatin profiling analysis reveals that C8orf33 antagonizes the chromatin association of KAT8 acetyltransferase at DSB sites leading to reduced histone 4 lysine 16 acetylation (H4K16ac) levels. Accordingly, the loss of C8orf33 enhances KAT8 chromatin binding, leading to elevated H4K16ac levels. This promotes the recruitment of HR factors while suppressing the accumulation of NHEJ factors at DSB sites, thereby favoring HR over NHEJ. We also demonstarte that the elevated HR activity in C8orf33-deficient cells causes genomic instability, as evidenced by accelerated loss of ribosomal DNA repeats and increased cell death. Collectively, these findings establish C8orf33 as a critical regulator of DSB repair pathway choice, safeguarding genomic integrity
HostingRepository	PRIDE
AnnounceDate	2025-10-29
AnnouncementXML	Submission_2025-10-29_07:40:41.952.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tamar Ziv
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monomethylated residue; phosphorylated residue; acetylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-09 05:41:43	ID requested
⏵ 1	2025-10-29 07:40:42	announced

Dataset with its publication pending

submitter keyword: acetylation, DNA double-strand break

Nabieh Ayoub
contact affiliation	Faculty of Biology, Technion Israel Institute of Technology
contact email	ayoubn@technion.ac.il
lab head
Tamar Ziv
contact affiliation	Technion
contact email	tamarz@technion.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062780
     1. Label: PRIDE project
     2. Name: C8orf33 dictates DNA double-strand break repair choice by modulating KAT8-mediated H4K16 acetylation