PXD002946

PXD002946 is an original dataset announced via ProteomeXchange.

Title	The Functions of Serine 687 Phosphorylation of Human DNA Polymerase eta in UV Damage Tolerance
Description	DNA polymerase  (pol) is a Y-family translesion synthesis polymerase that plays a key role in the cellular tolerance toward UV irradiation-induced DNA damage. Here, we identified, for the first time, the phosphorylation of serine 687 (S687), which islocated in the highly conserved nuclear localization signal (NLS) region of human pol and is mediated by cyclin-dependent kinase 2 (CDK2). We also showed that this phosphorylation is stimulated in human cells upon UV light exposure and results in diminished interaction of pol with proliferating cell nuclear antigen (PCNA). Furthermore, we demonstrated that the phosphorylation of S687 in polconfers cellular protection fromUV irradiation and increases the efficiency in replication across a site-specifically incorporated cyclobutane pyrimidine dimer in human cells. Based on these results, we proposed a mechanistic model where S687 phosphorylation functions in the reverse polymerase switching step of translesion synthesis: The phosphorylation brings negative charges to the NLS of pol, which facilitates its departure from PCNA, thereby resetting the replication fork for highly accurate and processive DNA replication. Thus, our study, together with previous findings, supported that the post-translational modifications of NLS of pol played a dual role in polymerase switching, where K682 deubiquitination promotes the recruitment of pol to PCNA immediately prior to lesion bypass and S687 phosphorylation stimulates its departure from the replication fork immediately after lesion bypass.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:26:20.301.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	xiaoxia dai
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2015-09-21 01:50:13	ID requested
1	2016-07-19 04:21:49	announced
⏵ 2	2024-10-22 04:26:28	announced	2024-10-22: Updated project metadata.

10.1074/mcp.M115.052167;

Dai X, You C, Wang Y, in UV Damage Tolerance. Mol Cell Proteomics, 15(6):1913-20(2016) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: translesion synthesis, CDK2,DNA polymerase eta

Yingsheng Wang
contact affiliation	University of California, Riverside
contact email	yinsheng.wang@ucr.edu
lab head
xiaoxia dai
contact affiliation	UCR
contact email	xiaoxiad@ucr.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002946
     1. Label: PRIDE project
     2. Name: The Functions of Serine 687 Phosphorylation of Human DNA Polymerase eta in UV Damage Tolerance