Ser8
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Home > Phosphorylation Site Page: > Ser8  -  RFA2 (human)

Site Information
MWNsGFEsyGsssyG   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 470083

In vivo Characterization
Methods used to characterize site in vivo:
electrophoretic mobility shift ( 27 , 37 ) , flow cytometry ( 14 , 35 ) , immunoassay ( 1 , 3 , 6 , 8 , 22 ) , immunoprecipitation ( 6 , 28 , 31 ) , mass spectrometry ( 14 , 30 ) , mutation of modification site ( 4 , 6 , 28 , 29 , 31 , 35 , 36 , 37 ) , phospho-antibody ( 1 , 2 , 3 , 5 , 6 , 7 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 29 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ) , western blotting ( 2 , 3 , 5 , 6 , 7 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 )
Disease tissue studied:
bone cancer ( 1 , 5 , 6 , 11 , 12 , 13 , 14 , 15 , 16 , 22 , 24 , 25 , 31 , 32 , 33 , 35 , 37 , 38 ) , brain cancer ( 5 , 29 ) , glioblastoma ( 5 , 29 ) , glioma ( 5 , 29 ) , breast cancer ( 5 , 11 , 38 ) , breast ductal carcinoma ( 5 ) , breast cancer, triple negative ( 5 ) , colorectal cancer ( 5 , 29 ) , colorectal carcinoma ( 5 , 29 ) , leukemia ( 27 ) , chronic myelogenous leukemia ( 27 ) , lung cancer ( 2 , 5 , 6 ) , non-small cell lung cancer ( 2 , 5 , 6 ) , non-small cell lung adenocarcinoma ( 2 , 5 , 6 ) , non-small cell large cell lung carcinoma ( 2 ) , squamous cell carcinoma of the oropharynx ( 8 ) , ovarian cancer ( 3 ) , pancreatic cancer ( 5 ) , pancreatic carcinoma ( 5 ) , multiple myeloma ( 9 ) , prostate cancer ( 5 ) , melanoma skin cancer ( 10 ) , cancer, squamous cell carcinoma ( 18 ) , Xeroderma pigmentosum ( 26 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
ATM (human) ( 29 ) , ATR (human) ( 21 , 29 , 37 ) , BAT1 (human) ( 3 ) , BRCA1 (human) ( 3 ) , CDC5L (human) ( 21 ) , CDK5 (human) ( 14 ) , Chk1 (human) ( 29 ) , CtIP (human) ( 21 ) , DKFZp686L1814 (human) ( 2 ) , DNAPK (human) ( 6 ) , FAM44A (human) ( 13 ) , FANCD2 (human) ( 12 , 23 ) , FOXM1 (human) ( 2 ) , HEL308 (human) ( 1 ) , MCPH1 (human) ( 38 ) , NBS1 (human) ( 36 ) , NONO (human) ( 10 ) , p21Cip1 (human) ( 6 ) , p53 (human) ( 6 ) , PARG (human) ( 17 ) , PIAS1 (human) ( 32 ) , PIAS4 (human) ( 32 ) , POLH (human) ( 26 ) , PPP4R2 (human) ( 31 ) , PRPF19 (human) ( 21 ) , PRPF3 (human) ( 21 ) , SIRT6 (human) ( 9 ) , TELO2 (human) ( 29 ) , TOPBP1 (human) ( 11 )
Putative in vivo kinases:
DNAPK (human) ( 29 , 34 , 35 )
Putative upstream phosphatases:
PPP4C (human) ( 31 )
Treatments:
4-nitroquinoline_1-oxide ( 29 ) , adriamycin ( 9 , 16 ) , aphidicolin ( 33 ) , AZ20 ( 22 ) , caffeine ( 33 ) , camptothecin ( 6 , 16 , 17 , 21 , 25 , 29 , 32 ) , carboplatin ( 26 ) , CGK733 ( 34 ) , cisplatin ( 26 , 27 , 34 ) , CPT ( 3 , 15 , 35 ) , etoposide ( 16 , 18 ) , gemcitabine ( 5 ) , HAMNO ( 18 ) , hydroxyurea ( 5 , 14 , 22 , 23 , 24 , 29 , 31 , 33 , 36 , 37 ) , ionizing_radiation ( 17 , 19 , 27 , 29 , 32 ) , KU-55933 ( 27 , 34 ) , mirin ( 5 ) , miRNA ( 15 ) , mitomycin_C ( 13 ) , MK-8776 ( 5 ) , MMS ( 29 ) , NU7026 ( 25 ) , NU7441 ( 27 , 34 ) , olaparib ( 11 ) , oxaliplatin ( 34 ) , prexasertib ( 2 ) , seliciclib ( 35 ) , siRNA ( 38 ) , UCN-01 ( 23 ) , UV ( 29 , 37 , 38 ) , VE-821 ( 24 , 25 )

Downstream Regulation
Effects of modification on RFA2:
intracellular localization ( 34 , 37 ) , molecular association, regulation ( 6 , 28 )
Effects of modification on biological processes:
apoptosis, induced ( 36 ) , cell cycle regulation ( 5 , 6 , 29 ) , cell growth, altered ( 37 ) , DNA repair, induced ( 3 , 6 , 28 ) , transcription, altered ( 6 )
Induce interaction with:
WRN (human) ( 28 ) , p53 (human) ( 6 )

Disease / Diagnostics Relevance
Relevant diseases:
squamous cell carcinoma of the oropharynx ( 8 )

References 

1

Anand R, et al. (2021) HELQ is a dual-function DSB repair enzyme modulated by RPA and RAD51. Nature
34937945   Curated Info

2

Branigan TB, et al. (2021) MMB-FOXM1-driven premature mitosis is required for CHK1 inhibitor sensitivity. Cell Rep 34, 108808
33657372   Curated Info

3

Xu Z, et al. (2020) Suppression of DDX39B sensitizes ovarian cancer cells to DNA-damaging chemotherapeutic agents via destabilizing BRCA1 mRNA. Oncogene
32989256   Curated Info

4

Liu L, et al. (2019) O-GlcNAcylation of Thr12 / Ser56 in short form O-GlcNAc transferase (sOGT) regulates its substrate selectivity. J Biol Chem
31527085   Curated Info

5

Warren N, Eastman A (2018) Inhibition of checkpoint kinase 1 following gemcitabine-mediated S phase arrest results in CDC7- and CDK2-dependent replication catastrophe. J Biol Chem
30573684   Curated Info

6

Romanova LY, Mushinski F, Kovalchuk AL (2018) Transcriptional activation of p21 contributes to suppression of HR by p53 in response to replication arrest induced by camptothecin. Oncotarget 9, 25427-25440
29875999   Curated Info

7

Hamperl S, et al. (2017) Transcription-Replication Conflict Orientation Modulates R-Loop Levels and Activates Distinct DNA Damage Responses. Cell 170, 774-786.e19
28802045   Curated Info

8

Rector J, et al. (2017) S4S8-RPA phosphorylation as an indicator of cancer progression in oral squamous cell carcinomas. Oncotarget 8, 9243-9250
27999209   Curated Info

9

Cea M, et al. (2016) Evidence for a role of the histone deacetylase SIRT6 in DNA damage response of multiple myeloma cells. Blood 127, 1138-50
26675349   Curated Info

10

Alfano L, et al. (2016) NONO regulates the intra-S-phase checkpoint in response to UV radiation. Oncogene 35, 567-76
25893301   Curated Info

11

Moudry P, et al. (2016) TOPBP1 regulates RAD51 phosphorylation and chromatin loading and determines PARP inhibitor sensitivity. J Cell Biol 212, 281-8
26811421   Curated Info

12

Schwab RA, et al. (2015) The Fanconi Anemia Pathway Maintains Genome Stability by Coordinating Replication and Transcription. Mol Cell 60, 351-61
26593718   Curated Info

13

Higgs MR, et al. (2015) BOD1L Is Required to Suppress Deleterious Resection of Stressed Replication Forks. Mol Cell 59, 462-77
26166705   Curated Info

14

Chiker S, et al. (2015) Cdk5 promotes DNA replication stress checkpoint activation through RPA-32 phosphorylation, and impacts on metastasis free survival in breast cancer patients. Cell Cycle 14, 3066-78
26237679   Curated Info

15

Hühn D, Kousholt AN, Sørensen CS, Sartori AA (2015) miR-19, a component of the oncogenic miR-17∼92 cluster, targets the DNA-end resection factor CtIP. Oncogene 34, 3977-84
25308476   Curated Info

16

Zellweger R, et al. (2015) Rad51-mediated replication fork reversal is a global response to genotoxic treatments in human cells. J Cell Biol 208, 563-79
25733714   Curated Info

17

Ray Chaudhuri A, Ahuja AK, Herrador R, Lopes M (2015) Poly(ADP-Ribosyl) glycohydrolase prevents the accumulation of unusual replication structures during unperturbed S phase. Mol Cell Biol 35, 856-65
25535335   Curated Info

18

Glanzer JG, et al. (2014) RPA inhibition increases replication stress and suppresses tumor growth. Cancer Res 74, 5165-72
25070753   Curated Info

19

Yamamoto Y, et al. (2014) A rare polymorphic variant of NBS1 reduces DNA repair activity and elevates chromosomal instability. Cancer Res 74, 3707-15
24830725   Curated Info

20

Hirokawa T, et al. (2014) CBP-93872 inhibits NBS1-mediated ATR activation, abrogating maintenance of the DNA double-strand break-specific G2 checkpoint. Cancer Res 74, 3880-9
24876101   Curated Info

21

Maréchal A, et al. (2014) PRP19 Transforms into a Sensor of RPA-ssDNA after DNA Damage and Drives ATR Activation via a Ubiquitin-Mediated Circuitry. Mol Cell 53, 235-46
24332808   Curated Info

22

Toledo LI, et al. (2013) ATR Prohibits Replication Catastrophe by Preventing Global Exhaustion of RPA. Cell 155, 1088-103
24267891   Curated Info

23

Lossaint G, et al. (2013) FANCD2 binds MCM proteins and controls replisome function upon activation of s phase checkpoint signaling. Mol Cell 51, 678-90
23993743   Curated Info

24

Couch FB, et al. (2013) ATR phosphorylates SMARCAL1 to prevent replication fork collapse. Genes Dev 27, 1610-23
23873943   Curated Info

25

Shiotani B, et al. (2013) Two Distinct Modes of ATR Activation Orchestrated by Rad17 and Nbs1. Cell Rep 3, 1651-62
23684611   Curated Info

26

Sokol AM, Cruet-Hennequart S, Pasero P, Carty MP (2013) DNA polymerase η modulates replication fork progression and DNA damage responses in platinum-treated human cells. Sci Rep 3, 3277
24253929   Curated Info

27

Prendergast ÁM, et al. (2011) Activation of DNA damage response pathways in human mesenchymal stem cells exposed to cisplatin or γ-irradiation. Cell Cycle 10, 3768-77
22037398   Curated Info

28

Machwe A, et al. (2011) Molecular cooperation between the Werner syndrome protein and replication protein A in relation to replication fork blockage. J Biol Chem 286, 3497-508
21107010   Curated Info

29

Liaw H, Lee D, Myung K (2011) DNA-PK-dependent RPA2 hyperphosphorylation facilitates DNA repair and suppresses sister chromatid exchange. PLoS One 6, e21424
21731742   Curated Info

30

Iliuk AB, et al. (2010) In-depth analyses of kinase-dependent tyrosine phosphoproteomes based on metal ion-functionalized soluble nanopolymers. Mol Cell Proteomics 9, 2162-72
20562096   Curated Info

31

Lee DH, et al. (2010) A PP4 phosphatase complex dephosphorylates RPA2 to facilitate DNA repair via homologous recombination. Nat Struct Mol Biol 17, 365-72
20154705   Curated Info

32

Galanty Y, et al. (2009) Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks. Nature 462, 935-9
20016603   Curated Info

33

Vassin VM, et al. (2009) Human RPA phosphorylation by ATR stimulates DNA synthesis and prevents ssDNA accumulation during DNA-replication stress. J Cell Sci 122, 4070-80
19843584   Curated Info

34

Cruet-Hennequart S, et al. (2008) Enhanced DNA-PK-mediated RPA2 hyperphosphorylation in DNA polymerase eta-deficient human cells treated with cisplatin and oxaliplatin. DNA Repair (Amst) 7, 582-96
18289945   Curated Info

35

Anantha RW, Vassin VM, Borowiec JA (2007) Sequential and Synergistic Modification of Human RPA Stimulates Chromosomal DNA Repair. J Biol Chem 282, 35910-23
17928296   Curated Info

36

Manthey KC, et al. (2007) NBS1 mediates ATR-dependent RPA hyperphosphorylation following replication-fork stall and collapse. J Cell Sci 120, 4221-9
18003706   Curated Info

37

Olson E, et al. (2006) RPA2 is a direct downstream target for ATR to regulate the S-phase checkpoint. J Biol Chem 281, 39517-33
17035231   Curated Info

38

Rai R, et al. (2006) BRIT1 regulates early DNA damage response, chromosomal integrity, and cancer. Cancer Cell 10, 145-57
16872911   Curated Info