Identifiers
ataxia telangiectasia and Rad3 related
HUGO:ATR HGNC:882 ENTREZ:545 UNIPROT:Q13535 GENECARDS:ATR REACTOME:405632 KEGG:545 ATLASONC:ATRID728ch3q23 WIKI:ATR
Maps_Modules
dnarepair
dnarepair
dnarepair
cellcycle
cellcycle
References
For S-phase checkpoint
PMID:11877377, PMID:15459660, PMID:17384638, PMID:17102137, PMID:17116885, PMID:17296725, PMID:19793801, PMID:17582221, PMID:18677104
HCLK2*/FANCM/FAAP24/active ATR complex inhibits S-phase
PMID:19282663, PMID:19622404
For ATR/ATRIP/CHEK1/Tim* S-phase checkpoint
PMID:15798197
References
d_re37( dnarepair ):
PMID:16332722, PMID:15136767
ATR binds stalled fork and phosphorylates CHK1 that activates checkpoint, stops cell cycle
d_re33:( dnarepair ) PMID:15485915
d_re43:( dnarepair ) PMID:16731533
d_re49:( dnarepair ) PMID:19788416
d_re71( dnarepair ):
For inactivation of EXO1 by 53BP1-mediated phosphorylation:
PMID:18756267, PMID:15867354
ATM and ATR phosphorylate EXO1 and lead to EXO1 ubiquitination and degradation:
PMID:18048416, PMID:11438669, PMID:20019063
d_re90( dnarepair ):
PMID:9488723, PMID:19772495
PMID:17303408
d_re110( dnarepair ):
Phosphorylation by ATM and ATR at T847, S327
Phosphorylation at S327 by ATM and ATR are essential for shift from A_NHEJ to HR
Phosphorylation by CDC2(CDK1) in cell cycle dep manner to shift from C_NHEJ ot HR at: Ser 267
This phosphorylation allows resection that initiates HR and blocks binding of Ku70/Ku80 complex that initiates C_NHEJ.
PMID:19357644, PMID:15485915, PMID:19490890, PMID:18716619 (for CDK-dep phosph), PMID:20051983
BRCA1 and CtIP interactions make shift from A_NHEJ and C_NHEJ toward HR
Resected DNA in HR is a positive trigger for amplification of the HR pathway (positive loop):
PMID:20051983
Only when CDKs are fully active, this fully activates HR during S and G2 phases:
PMID:18511906, PMID:18716619
d_re132:( dnarepair ) PMID:19841479, PMID:19793861
d_re160( dnarepair ):
PMID:18931676
PMID:19686080
Link between cell cycle and activation of Fanconi pathway
d_re186( dnarepair ):
PMID:18931676, PMID:19686080
d_re187( dnarepair ):
NBS1 is required for FANCD2 phosphorylation and relocation into the FA core complex:
PMID:14988723
d_re199( dnarepair ):
HCLK2*/FANCM/FAAP24/active ATR complex inhibit S-phase:
PMID:19282663, PMID:19622404, PMID:18995830
d_re205( dnarepair ):
Phosphorylation of NBS1 by ATR in response to crosslink-activation of S phase checkpoint
PMID:15136767, PMID:14988723
d_re206( dnarepair ):
Phosphorylation of NBS1 bt ATR in responce to crosslink-activation of S phase checkpoint
PMID:15136767
Formation of the complex for crosslink-activation of S phase checkpoint. FA core complex activates the reaction to stop cell cycle propagation:
d_re235( dnarepair ):
ATR phosphorylates XPA and activates NER during S-phase in response to damaged DNA, but not during other cc phases:
PMID:16540648, PMID:19004803
d_re260( dnarepair ):
DNA with O6-methylguanine adducts, MutSalpha and MutLalpha activate ATR/ATRIP and BER pathways performs the repair:
PMID:16713580, PMID:18543256
Damaged DNA triggers ATR/ATRIP complex activation
d_re315:( dnarepair ) PMID:16885023, PMID:17303408
d_re408:( dnarepair ) PMID:9858600
References
d_re37( dnarepair ):
PMID:16332722, PMID:15136767
ATR binds stalled fork and phosphorylates CHK1 that activates checkpoint, stops cell cycle
+ FAAP24*@default + FANCM@default + ATR|pho|active@Nucleus → ATR|pho:FAAP24*:FANCM:HCLK2*@default
+ MRE11*:NBS1*|S343_pho:RAD50@default + ATR|pho|active@Nucleus → ATR|pho:FANCD2|K561_ubi|pho:MRE11*:NBS1*|S343_pho:RAD50@default
+ ATRIP@default → ATRIP:ATR|pho@default
+ ATRIP:ATR|pho@default + CLSPN|pho@default + RAD17|pho@default → ATRIP:ATR|pho:CLSPN|pho:RAD17|pho:TOPBP1@default
→ ATR|pho|active@Nucleus
+ CLSPN|pho@default + RPA1:RPA2:RPA3@default → ATRIP:ATR|pho:CLSPN|pho:RPA1:RPA2:RPA3@default
+ CLSPN|pho@default + ATRIP:ATR|pho@default + CHEK1|pho|active@default → ATRIP:ATR|pho:CHEK1|pho:CLSPN|pho:HCLK2*@default
+ CLSPN|pho@default + PCNA|K164_ubi@default + ATRIP:ATR|pho@default + CHEK1|pho|active@Nucleus → ATRIP:ATR|pho:CHEK1|pho:CLSPN|pho:PCNA|K164_ubi:TIM1*@default
+ TIPIN@default + TIM1*@default + CHEK1|pho|active@default → ATRIP:ATR|pho:CHEK1|pho:CLSPN|pho:RPA1:RPA2:RPA3:TIM1*:TIPIN@default
→ CTIP*|emp|S372_pho|T847_pho|S267_pho@default
→ G2 phase@default
→ M phase@default
→ SMARCAL1|pho@default
→ FANCI|pho@default
→ gRepaired_DNA*@Nucleus
→ FANCA|pho@default
→ FANCD2|pho@default
→ FANCG|S7_pho@default
→ NBS1*|S343_pho@default
→ XPA|S196_pho@Nucleus
→ RAD17|pho@default
→ CHEK1|pho|active@default
+ MCM2:MCM3:MCM4:MCM5:MCM6:MCM7@default + CDT1@default + CDC6@default + CDC45@default + POLA*@default + PRIM*@default + RPA1@Nucleus + RPA2@Nucleus + RPA3@Nucleus → CDC45:CDC6:CDT1:MCM2:MCM3:MCM4:MCM5:MCM6:MCM7:ORC1*:ORC2*:ORC3*:ORC4*:ORC5*:ORC6*:POLA*:PRIM*:RPA1:RPA2:RPA3@default
→ CTBP*|S181_pho|T179_pho|S185_pho@default
→ BRCA1|S988_pho|S1387_pho|S1423_pho|S1497_pho|S1524_pho|active@default
→ PARP1|PolyADPribose_unk|pho@Nucleus
→ RPA2|pho@default
→ DNA replicarion@default
→ SMC1*|S957_pho|S966_pho@default
→ SMC3|S1083_pho@default
+ RAD9*|pho@default + HUS1@default → HUS1:RAD1:RAD9*|pho@default
+ RAD17@default + RFC*@Nucleus → HUS1:RAD1:RAD17:RAD9*:RFC*@default
→ CLSPN|pho@default
→ MDM2|pho@default
→ gBER_M-glyc_DNA_st2*@Nucleus + Base@default
→ SIAH*|pho@default
→ PARP2|unk|pho@default
→ EXO1|S692_pho|S372_pho|S567_pho|S587_pho@default
→ CHEK2|pho|active@default
→ H2AFX|S139_pho@default