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PXD044258

PXD044258 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCatalytic and non-catalytic functions of DNA polymerase kappa in translesion DNA synthesis
DescriptionTranslesion DNA synthesis (TLS) is a cellular process that enables the bypass of DNA lesions encountered during DNA replication and is emerging as a primary target of chemotherapy. Among vertebrate DNA polymerases, polymerase kappa (PolK) has the distinctive ability to bypass minor groove DNA adducts in vitro. However, PolK is also required for cells to overcome major groove DNA adducts but the basis of this requirement is unclear. Here, we combine CRISPR base editor screening technology in human cells with TLS analysis of defined DNA lesions in Xenopus egg extracts to unravel the functions and regulations of PolK during lesion bypass. Strikingly, we show that PolK has two main functions during TLS, which are differentially regulated via Rev1 binding. On the one hand, PolK is essential to replicate across a minor groove DNA lesion in a process that depends on PCNA ubiquitylation but is independent of Rev1. On the other hand, via its cooperative interaction with Rev1 and ubiquitylated PCNA, PolK appears to stabilize the Rev1-PolZ extension complex on DNA to allow extension past major groove DNA lesions and abasic sites, in a process that is independent of PolK's catalytic activity. Together, our work identifies catalytic and non-catalytic functions of PolK in TLS and reveals important regulatory mechanisms underlying the unique domain architecture present at the C-terminal end of Y-family TLS polymerases.
HostingRepositoryPRIDE
AnnounceDate2024-08-27
AnnouncementXMLSubmission_2024-08-27_05:15:37.757.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterIvo Hendriks
SpeciesList scientific name: Xenopus laevis (African clawed frog); NCBI TaxID: 8355;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-08-01 04:45:03ID requested
12024-08-27 05:15:38announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Xenopus, TLS, Polz, Polk, Rev1, polymerase kappa, ubiquitin, translesion DNA synthesis, PCNA, DNA replication
Contact List
Ivo Hendriks
contact affiliationProteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
contact emailivo.a.hendriks@gmail.com
lab head
Ivo Hendriks
contact affiliationProteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
contact emailivo.a.hendriks@gmail.com
dataset submitter
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Dataset FTP location
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