Reactome | Activation of CHEK1 at resected DNA DSBs

Activation of CHEK1 at resected DNA DSBs

Stable Identifier

R-HSA-5684887

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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Activation of CHEK1 at resected DNA DSBs

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CHEK1 (Chk1) is a checkpoint kinase activated during genotoxic stress. CHEK1 activation at resected DNA double-strand breaks (DSBs) involves ATR-mediated phosphorylation of CHEK1 serine residues S317 and S345 in the presence of claspin (CLSPN), TOPBP1, RAD17:RFC complex, RAD9:HUS1:RAD1 complex, TIMELESS:TIPIN complex, RPA complex and RHNO1 (Liu et al. 2000, Zhao and Piwnica-Worms 2001, Kumagai and Dunphy 2003, Sorensen et al. 2004, Wang et al. 2006, Kemp et al. 2010, Cotta-Ramusino et al. 2011, Liu et al. 2012). Following phosphorylation, CHEK1 dissociates from chromatin and phosphorylates target proteins involved in S/G2 checkpoint activation and/or homologous recombination repair (Smits et al. 2006). CLSPN needs to interact with chromatin only transiently in order to facilitate CHEK1 activation (Lee et al. 2005).

Literature References

PubMed ID	Title	Journal	Year
10859164	Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Bradley, A, Donehower, LA, Tamai, K, Carattini-Rivera, S, Elledge, SJ, DeMayo, F, Cortez, D, Luo, G, Guntuku, S, Cui, XS, Matsuoka, S, Liu, Q	Genes Dev	2000
16148040	Roles of replication fork-interacting and Chk1-activating domains from Claspin in a DNA replication checkpoint response Gold, DA, Shevchenko, A, Dunphy, WG, Shevchenko, A, Lee, J	Mol Biol Cell	2005
16885023	Rad17 phosphorylation is required for claspin recruitment and Chk1 activation in response to replication stress Li, L, Elledge, SJ, Wang, X, Hittelman, WN, Zou, L, Lu, T, Bao, S, Hurov, KE	Mol. Cell	2006
20233725	Tipin-replication protein A interaction mediates Chk1 phosphorylation by ATR in response to genotoxic stress Kaufmann, WK, Grillo, M, Yilmaz, S, Abraham, RT, Cordeiro-Stone, M, Sancar, A, Kang, TH, Kemp, MG, Akan, Z, Unsal-Kaçmaz, K, Smith-Roe, SL	J. Biol. Chem.	2010
22977173	Distinct roles for DNA-PK, ATM and ATR in RPA phosphorylation and checkpoint activation in response to replication stress Troksa, K, Shrivastav, M, Amerin, C, Nickoloff, JA, Oakley, GG, Liu, S, Ashley, AK, Glanzer, JG, Manthey, K, Opiyo, SO	Nucleic Acids Res.	2012
15190204	ATR, Claspin and the Rad9-Rad1-Hus1 complex regulate Chk1 and Cdc25A in the absence of DNA damage Sorensen, CS, Syljuasen, RG, Lukas, J, Bartek, J	Cell Cycle	2004
11390642	ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1 Zhao, H, Piwnica-Worms, H	Mol Cell Biol	2001
21659603	A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1 interacting protein required for ATR signaling Hurov, K, Elledge, SJ, Cotta-Ramusino, C, McDonald, ER, Sowa, ME, Harper, JW	Science	2011
16360315	Rapid PIKK-Dependent Release of Chk1 from Chromatin Promotes the DNA-Damage Checkpoint Response Smits, VA, Jackson, SP, Reaper, PM	Curr Biol	2006
12545175	Repeated phosphopeptide motifs in Claspin mediate the regulated binding of Chk1 Kumagai, A, Dunphy, WG	Nat Cell Biol	2003

Participants

Input

Output

Participates

as an event of

Processing of DNA double-strand break ends (Homo sapiens)

Event Information

Go Biological Process

DNA replication (0006260)

Catalyst Activity

protein serine/threonine kinase activity of ATR:ATRIP:p-RPA:3' overhanging ssDNA-DSBs:p-MRN:p-S1981,Ac-K3016-ATM:KAT5:BRCA1-C complex:EXO1,DNA2:BLM,WRN:p-S990,Ac-K1249-BRIP1:RAD17:RFC:RAD9:HUS1:RAD1:RHNO1:TOPBP1:TIMELESS:TIPIN:p-T916,S945-CLSPN:CHEK1 [nucleoplasm]

Physical Entity

ATR:ATRIP:p-RPA:3' overhanging ssDNA-DSBs:p-MRN:p-S1981,Ac-K3016-ATM:KAT5:BRCA1-C complex:EXO1,DNA2:BLM,WRN:p-S990,Ac-K1249-BRIP1:RAD17:RFC:RAD9:HUS1:RAD1:RHNO1:TOPBP1:TIMELESS:TIPIN:p-T916,S945-CLSPN:CHEK1 [nucleoplasm] (Homo sapiens)

Activity

protein serine/threonine kinase activity (GO:0004674)

Orthologous Events

Activation of CHEK1 at resected DNA DSBs (Canis familiaris)

Activation of CHEK1 at resected DNA DSBs (Drosophila melanogaster)

Activation of CHEK1 at resected DNA DSBs (Mus musculus)

Activation of CHEK1 at resected DNA DSBs (Rattus norvegicus)

Activation of CHEK1 at resected DNA DSBs (Sus scrofa)

Authored

Orlic-Milacic, M (2015-05-12)