PXD066315

PXD066315 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 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_22:19:38.203.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Miguel Hernandez Quiles
SpeciesList	scientific name: Xenopus laevis (African clawed frog); NCBI TaxID: 8355;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-18 08:12:11	ID requested
⏵ 1	2025-09-28 22:19:39	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: DNA polymerase kappa, acrolein-ICL, Translesion synthesis, Fanconi anemia pathway,acetaldehyde-ICL

Miguel Hernandez-Quiles
contact affiliation	Netherlands Cancer Institute, Amsterdam, Netherlands.
contact email	m.hernandez@nki.nl
lab head
Miguel Hernandez Quiles
contact affiliation	Netherlands Cancer Institute
contact email	m.hernandez@nki.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066315
     1. Label: PRIDE project
     2. Name: DNA polymerase kappa is the primary translesion synthesis polymerase for aldehyde ICLs