PXD062134

PXD062134 is an original dataset announced via ProteomeXchange.

Title	DNA polymerase kappa is the primary translesion synthesis polymerase for aldehyde ICLs
Description	DNA interstrand crosslinks (ICLs) are highly cytotoxic lesions that block essential cellular processes like replication and transcription. Endogenous ICLs can be induced by reactive aldehydes produced during normal cellular metabolism. Defective repair of these aldehyde-induced ICLs is associated with Fanconi anemia (FA), a cancer predisposition syndrome. We previously showed that acetaldehyde-induced ICLs are repaired by the Fanconi anemia (FA) pathway and a novel excision-independent pathway. Here, we demonstrate that ICLs induced by acrolein, another cellular aldehyde, are also repaired by both pathways, establishing the generality of aldehyde ICL repair. Focusing on the FA pathway, we identify DNA polymerase kappa (Polκ) as the primary translesion synthesis (TLS) polymerase responsible for the insertion step during lesion bypass of unhooked aldehyde ICLs. This function requires Polκ's catalytic activity and PCNA interaction domains, but is independent of Rev1 interaction. In contrast, Polκ has a minor, non-catalytic role in the extension step of cisplatin ICL repair that is dependent on Rev1 interaction. Our work reveals a key role for Polκ in aldehyde ICL repair and provides mechanistic insights into how different ICL structures determine the choice of TLS polymerases during repair.
HostingRepository	PRIDE
AnnounceDate	2025-09-29
AnnouncementXML	Submission_2025-09-28_17:03:19.492.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Roxanne Van Der Sluijs
SpeciesList	scientific name: Xenopus laevis (African clawed frog); NCBI TaxID: 8355;
ModificationList	monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-21 14:56:07	ID requested
⏵ 1	2025-09-28 17:03:20	announced

van der Sluijs RV, Verkennis AEE, Hodskinson MR, Barnett J, Cruz VM, Hernandez-Quiles M, Liolios T, Morton SB, Hendrikx A, Bos C, Post H, Millington CL, Rouillon C, Ricci G, Mattiroli F, Williams DM, Altelaar M, Vermeulen M, Patel KJ, Knipscheer P, DNA polymerase kappa is the primary translesion synthesis polymerase for aldehyde ICLs. Nucleic Acids Res, 53(18):(2025) [pubmed]

10.1093/nar/gkaf875;

submitter keyword: Acrolein-ICL, FA pathway,Acetaldehyde-ICL, polymerase kappa, Translesion Synthesis

Puck Knipscheer
contact affiliation	Oncode Institute, Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, Utrecht, 3584 CT, The Netherlands
contact email	p.knipscheer@hubrecht.eu
lab head
Roxanne Van Der Sluijs
contact affiliation	Hubrecht Institute
contact email	r.sluijs@hubrecht.eu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/09/PXD062134

PRIDE project URI

• PRIDE
  1. PXD062134
     1. Label: PRIDE project
     2. Name: DNA polymerase kappa is the primary translesion synthesis polymerase for aldehyde ICLs