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BRCA1-associated genome surveillance complex (BASC)

Function: - role as a sensor of abnormal DNA structures &/or as a regulator of post-replication repair processes (putative) Structure: - large molecular complex which includes tumor suppressors & DNA repair proteins - subunits: BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 & the RAD50-MRE11-NBS1 complex

General

molecular complex

Properties

SUBUNITS: BRCA1 protein COMPARTMENT: cell nucleus MOTIF: Zn finger C4-type SITE: 24-64 EFFECTOR-BOUND: Zn+2 phosphorylation site BRCA1 C-terminal (BRCT) motif DNA mismatch repair protein Msh2 MOTIF: EXO1 interaction {601-671} ATP-binding site NAME: ATP-binding site SITE: 669-676 Ser phosphorylation site {S860} DNA mismatch repair protein Msh6 COMPARTMENT: cell nucleus MOTIF: Ser phosphorylation site {S14} alanine-rich region {34-37} MOTIF: alanine residue (SEVERAL) Ser phosphorylation site {S41} Ser phosphorylation site {S43} Ser phosphorylation site {S79} Ser phosphorylation site {S91} PWWP domain {92-154} MOTIF: Ser phosphorylation site {S137} Thr phosphorylation site {T139} Ser phosphorylation site {S200} glutamate-rich region {201-209} MOTIF: glutamate residue (SEVERAL) Ser phosphorylation site {S219} Ser phosphorylation site {S227} Ser phosphorylation site {S252} Ser phosphorylation site {S254} Ser phosphorylation site {S256} Ser phosphorylation site {S261} Ser phosphorylation site {S309} Ser phosphorylation site {S348} Ser phosphorylation site {S830} Thr phosphorylation site {T924} glutamate-rich region {1118-1123} MOTIF: glutamate residue (SEVERAL) ATP-binding site NAME: ATP-binding site SITE: 1134-1141 DNA mismatch repair protein Mlh1 MOTIF: EXO1 interaction {410-650} MOTIF: Ser phosphorylation site {S477} ATM protein MOTIF: Thr phosphorylation site {T72} Ser phosphorylation site {S85} Thr phosphorylation site {T86} Ser phosphorylation site {S367} Thr phosphorylation site {T373} interaction with ABL1 {1373-1382} FAT domain NAME: FAT domain SITE: 1960-2566 MOTIF: Tyr phosphorylation site binding site FOR-BINDING-OF: Paxillin Ser phosphorylation site {S1981} Thr phosphorylation site {T1985} PI3K/PI4K {2712-2962} FATC {3024-3056} STATE: active state BLM protein MOTIF: Ser phosphorylation site {S48} Ser phosphorylation site {S53} Thr phosphorylation site {T57} Thr phosphorylation site {T114} serine-rich region {310-316} MOTIF: serine residue (SEVERAL) Ser phosphorylation site {S358} Ser phosphorylation site {S419} Ser phosphorylation site {S422} Ser phosphorylation site {S480} Ser phosphorylation site {S499} Thr phosphorylation site {T508} helicase NAME: helicase SITE: 676-851 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 689-696 DEAD/H box NAME: DEAD/H box SITE: 795-798 Helicase C-terminal {877-1024} HRDC {1212-1292} Ser phosphorylation site {S1295} Ser phosphorylation site {S1296} Ser phosphorylation site {S1303} Ser phosphorylation site {S1310} nuclear translocation signal {1334-1349} nibrin MOTIF: forkhead-associated (FHA) domain {24-83} BRCA1 C-terminal (BRCT) motif SITE: 105-181 Ser phosphorylation site {S278} Thr phosphorylation site {T337} Ser phosphorylation site {S341} Ser phosphorylation site {S343} Ser phosphorylation site {S397} Ser phosphorylation site {S432} glutamine-rich region {448-451} MOTIF: glutamine residue (SEVERAL) nuclear translocation signal {461-467} Thr phosphorylation site {T602} Ser phosphorylation site {S615} EEXXXDDL {736-743} double-strand break repair protein MRE11A COMPARTMENT: cell nucleus MOTIF: Thr phosphorylation site {T74} histidine residue {H129} Ser phosphorylation site {S649} Ser phosphorylation site {S678} Ser phosphorylation site {S688} Ser phosphorylation site {S689} DNA repair protein RAD50 COMPARTMENT: cell nucleus MOTIF: ATP-binding site NAME: ATP-binding site SITE: 36-43 coiled coil {228-359} MOTIF: Ser phosphorylation site {S237} coiled coil {401-598} Zinc-hook {635-734} MOTIF: coiled coil {635-673} Ser phosphorylation site {S635} Ser phosphorylation site {S640} Zn+2-binding site SITE: 681-681 Zn+2-binding site SITE: 684-684 Thr phosphorylation site {T690} coiled coil {706-734} coiled coil {789-1079} replication factor-C

References

  1. Wang Y et al. BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Genes & Development 14:927-39, 2000 PMID: 10783165

Components

ATM protein (Ataxia Telangiectasia mutated) Bloom syndrome protein; recQ protein-like 3; DNA helicase, recQ-like type 2 (BLM, RECQ2, RECQL3) breast cancer type 1 susceptibility protein (BRCA1) DNA mismatch repair protein Mlh1; mutL protein homolog 1 (MLH1, COCA2) DNA mismatch repair protein Msh2; hMSH2; mutS protein homolog 2 (MSH2) DNA mismatch repair protein Msh6; hMSH6; mutS-alpha 160 kD subunit; p160; G/T mismatch-binding protein; GTMBP; GTBP (MSH6 GTBP) DNA repair protein RAD50; hRAD50 (RAD50) double-strand break repair protein MRE11A; meiotic recombination 11 homolog A; MRE11 homolog A; meiotic recombination 11 homolog 1; MRE11 homolog 1 (MRE11A, HNGS1, MRE11) nibrin; Nijmegen breakage syndrome protein 1; cell cycle regulatory protein p95 (NBN, NBS, NBS1, P95) replication factor-C