CTF18 interacts with replication protein A in response to replication stress

Kaneko,Yuta; Daitoku,Hiroaki; Komeno,Chihiro; Fukamizu,Akiyoshi

doi:10.3892/mmr.2016.5262

CTF18 interacts with replication protein A in response to replication stress

Authors:
- Yuta Kaneko
- Hiroaki Daitoku
- Chihiro Komeno
- Akiyoshi Fukamizu
View Affiliations

Affiliations: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305‑8577, Japan
Published online on: May 13, 2016 https://doi.org/10.3892/mmr.2016.5262
Pages: 367-372

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Replication stress response is a protective mechanism against defects in chromosome replication for maintaining genome integrity in eukaryotic cells. An alternative clamp loader complex termed chromosome transmission fidelity protein 18 and replication factor C (CTF18‑RFC) has been shown to act as a positive regulator of two types of replication stress response: S‑phase checkpoint signaling and translesion DNA synthesis. However, it remains largely unknown how CTF18‑RFC responds to replication stress and is recruited to stalled replication forks. The present study demonstrated that endogenous CTF18 forms a physical complex with a single‑stranded DNA‑binding protein replication protein A (RPA) in mammalian cells. Using an in situ proximity ligation assay (PLA), it was demonstrated that the interaction between CTF18 and RPA occurs in chromatin when replication stress is elicited by treatment with hydroxyurea during S phase. Similar results were obtained after exposure to ultraviolet irradiation, which triggers translesion DNA synthesis. Furthermore, the PLA demonstrated that the kinetics of the interaction between CTF18 and RPA was positively correlated with that of checkpoint kinase 1 phosphorylation, which is an indicator of activation of the ATM and Rad3‑related pathway. These findings provide novel insights into the molecular mechanism underlying the participation of CTF18‑RFC in the regulation of replication stress response.

View Figures

View References

1	Branzei D and Foiani M: Regulation of DNA repair throughout the cell cycle. Nat Rev Mol Cell Biol. 9:297–308. 2008. View Article : Google Scholar : PubMed/NCBI
2	Zeman MK and Cimprich KA: Causes and consequences of replication stress. Nat Cell Biol. 16:2–9. 2014. View Article : Google Scholar
3	Zou L and Elledge SJ: Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science. 300:1542–1548. 2003. View Article : Google Scholar : PubMed/NCBI
4	Choi JH, Lindsey-Boltz LA, Kemp M, Mason AC, Wold MS and Sancar A: Reconstitution of RPA-covered single-stranded DNA-activated ATR-Chk1 signaling. Proc Natl Acad Sci USA. 107:13660–13665. 2010. View Article : Google Scholar : PubMed/NCBI
5	Smits VA and Gillespie DA: DNA damage control: Regulation and functions of checkpoint kinase 1. FEBS J. 282:3681–3692. 2015. View Article : Google Scholar : PubMed/NCBI
6	Yang W: An overview of Y-Family DNA polymerases and a case study of human DNA polymerase eta. Biochemistry. 53:2793–2803. 2014. View Article : Google Scholar : PubMed/NCBI
7	Davies AA, Huttner D, Daigaku Y, Chen S and Ulrich HD: Activation of ubiquitin-dependent DNA damage bypass is mediated by replication protein a. Mol Cell. 29:625–636. 2008. View Article : Google Scholar : PubMed/NCBI
8	Watanabe K, Tateishi S, Kawasuji M, Tsurimoto T, Inoue H and Yamaizumi M: Rad18 guides poleta to replication stalling sites through physical interaction and PCNA monoubiquitination. EMBO J. 23:3886–3896. 2004. View Article : Google Scholar : PubMed/NCBI
9	Despras E, Daboussi F, Hyrien O, Marheineke K and Kannouche PL: ATR/Chk1 pathway is essential for resumption of DNA synthesis and cell survival in UV-irradiated XP variant cells. Hum Mol Genet. 19:1690–1701. 2010. View Article : Google Scholar : PubMed/NCBI
10	García-Rodríguez LJ, De Piccoli G, Marchesi V, Jones RC, Edmondson RD and Labib K: A conserved Polε binding module in Ctf18-RFC is required for S-phase checkpoint activation downstream of Mec1. Nucleic Acids Res. 43:8830–8838. 2015. View Article : Google Scholar
11	Shiomi Y, Masutani C, Hanaoka F, Kimura H and Tsurimoto T: A second proliferating cell nuclear antigen loader complex, Ctf18-replication factor C, stimulates DNA polymerase eta activity. J Biol Chem. 282:20906–20914. 2007. View Article : Google Scholar : PubMed/NCBI
12	Crabbé L, Thomas A, Pantesco V, De Vos J, Pasero P and Lengronne A: Analysis of replication profiles reveals key role of RFC-Ctf18 in yeast replication stress response. Nat Struct Mol Biol. 17:1391–1397. 2010. View Article : Google Scholar : PubMed/NCBI
13	Kubota T, Hiraga S, Yamada K, Lamond AI and Donaldson AD: Quantitative proteomic analysis of chromatin reveals that Ctf18 acts in the DNA replication checkpoint. Mol Cell Proteomics. 10:M1102011. View Article : Google Scholar : PubMed/NCBI
14	Mailand N, Gibbs-Seymour I and Bekker-Jensen S: Regulation of PCNA-protein interactions for genome stability. Nat Rev Mol Cell Biol. 14:269–282. 2013. View Article : Google Scholar : PubMed/NCBI
15	Kanellis P, Agyei R and Durocher D: Elg1 forms an alternative PCNA-interacting RFC complex required to maintain genome stability. Curr Biol. 13:1583–1595. 2003. View Article : Google Scholar : PubMed/NCBI
16	Bellaoui M, Chang M, Ou J, Xu H, Boone C and Brown GW: Elg1 forms an alternative RFC complex important for DNA replication and genome intergrity. EMBO J. 22:4304–4313. 2003. View Article : Google Scholar : PubMed/NCBI
17	Parrilla-Castellar ER, Arlander SJ and Karnitz L: Dial 9-1-1 for DNA damage: The Rad9-Hus1-Rad1 (9-1-1) clamp complex. DNA Repair (Amst). 3:1009–1014. 2004. View Article : Google Scholar
18	Hanna JS, Kroll ES, Lundblad V and Spencer FA: Saccharomyces cerevisiae CTF18 and CTF4 are required for sister chromatid cohesion. Mol Cell Biol. 21:3144–3158. 2001. View Article : Google Scholar : PubMed/NCBI
19	Taniguchi T, Garcia-Higuera I, Andreassen PR, Gregory RC, Grompe M and D'Andrea AD: S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51. Blood. 100:2414–2420. 2002. View Article : Google Scholar : PubMed/NCBI
20	Yamagata K, Daitoku H, Takahashi Y, Namiki K, Hisatake K, Kako K, Mukai H, Kasuya Y and Fukamizu A: Arginine methylation of FOXO transcription factors inhibits their phosphorylation by Akt. Mol Cell. 32:221–231. 2008. View Article : Google Scholar : PubMed/NCBI
21	Vassin VM, Anantha RW, Sokolova E, Kanner S and Borowiec JA: Human RPA phosphorylation by ATR stimulates DNA synthesis and prevents ssDNA accumulation during DNA-replication stress. J Cell Sci. 122:4070–4080. 2009. View Article : Google Scholar : PubMed/NCBI
22	Fan J and Pavletich NP: Structure and conformational change of a replication protein A heterotrimer bound to ssDNA. Genes Dev. 26:2337–2347. 2012. View Article : Google Scholar : PubMed/NCBI
23	Söderberg O, Gullberg M, Jarvius M, Ridderstråle K, Leuchowius KJ, Jarvius J, Wester K, Hydbring P, Bahram F, Larsson LG and Landegren U: Direct observation of individual endogenous protein complexes in situ by proximity ligation. Nat Methods. 3:995–1000. 2006. View Article : Google Scholar : PubMed/NCBI
24	Gullberg M and Andersson AC: Visualization and quantification of protein-protein interactions in cells and tissues. Nat Methods. 72010.
25	Mazouzi A, Velimezi G and Loizou JI: DNA replication stress: Causes, resolution and disease. Exp Cell Res. 329:85–93. 2014. View Article : Google Scholar : PubMed/NCBI
26	Liaw H, Lee D and Myung K: DNA-PK-dependent RPA2 hyperphosphorylation facilitates DNA repair and suppresses sister chromatid exchange. PLoS One. 6:e214242011. View Article : Google Scholar : PubMed/NCBI
27	Liu S, Opiyo SO, Manthey K, Glanzer JG, Ashley AK, Amerin C, Troksa K, Shrivastav M, Nicholoff JA and Oakley GG: Distinct roles for DNA-PK, ATM and ATR in RPA phosphorylation and checkpoint activation in response to replication stress. Nucleic Acids Res. 40:10780–10794. 2012. View Article : Google Scholar : PubMed/NCBI
28	Olson E, Nievera CJ, Klimovich V, Fanning E and Wu X: RPA2 is a direct downstream target for ATR to regulate the S-phase checkpoint. J Biol Chem. 281:39517–39533. 2006. View Article : Google Scholar : PubMed/NCBI
29	Maréchal A and Zou L: RPA-coated single-stranded DNA as a platform for post-translational modifications in the DNA damage response. Cell Res. 25:9–23. 2015. View Article : Google Scholar :
30	Vassin VM, Wold MS and Borowiec JA: Replication protein A (RPA) phosphorylation prevents RPA association with replication centers. Mol Cell Biol. 24:1930–1943. 2004. View Article : Google Scholar : PubMed/NCBI
31	Wu X, Shell SM and Zou Y: Interaction and colocalization of Rad9/Rad1/Hus1 checkpoint complex with replication protein A in human cells. Oncogene. 24:4728–4735. 2005. View Article : Google Scholar : PubMed/NCBI
32	Wu X, Yang Z, Liu Y and Zou Y: Preferential localization of hyperphosphorylated replication protein A to double-strand break repair and checkpoint complexes upon DNA damage. Biochem J. 391:473–480. 2005. View Article : Google Scholar : PubMed/NCBI
33	Kubota T, Nishimura K, Kanemaki MT and Donaldson AD: The Elg1 replication factor C-like complex functions in PCNA unloading during DNA replication. Mol Cell. 50:273–280. 2013. View Article : Google Scholar : PubMed/NCBI
34	Lee KY, Fu H, Aladjem MI and Myung K: ATAD5 regulates the lifespan of DNA replication factories by modulating PCNA level on the chromatin. J Cell Biol. 200:31–44. 2013. View Article : Google Scholar : PubMed/NCBI
35	Bylund GO and Burgers PM: Replication protein A-directed unloading of PCNA by the Ctf18 cohesion establishment complex. Mol Cell Biol. 25:5445–5455. 2005. View Article : Google Scholar : PubMed/NCBI