FANCM is a large (~250 kDa) DEAH-box family DNA-dependent ATPase and ATP-dependent DNA translocase that acts at stalled replication forks and DNA interstrand crosslinks (ICLs) to maintain genome stability. It is the most conserved Fanconi anemia protein, orthologous to archaeal Hef and to yeast Mph1/Fml1. Its N-terminal SF2 helicase/translocase domain (Walker A ATP-binding site, catalytic Lys117) uses ATP hydrolysis to translocate on duplex DNA and to catalyze branch migration of replication forks and Holliday junctions, thereby remodeling branched replication/recombination intermediates. Its catalytically dead C-terminal ERCC4/XPF-like domain heterodimerizes with FAAP24, and a central region binds the MHF1-MHF2 histone-fold dimer (CENPS-CENPX); the MHF dimer stimulates FANCM DNA binding and fork remodeling. Through these interactions FANCM anchors the Fanconi anemia core complex to chromatin at sites of replication stress, which is required for efficient DNA damage-induced monoubiquitination of the FANCD2-FANCI complex and for ATR checkpoint signaling. FANCM also promotes replication traverse of ICLs and suppresses sister-chromatid exchange and crossover recombination, acting as a regulator of homologous recombination rather than a core HR enzyme. The protein is nuclear and chromatin-bound, becomes hyperphosphorylated in response to genotoxic stress, and is highly expressed in germ cells; biallelic loss-of-function causes spermatogenic failure and premature ovarian failure.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0036297 interstrand cross-link repair | IBA GO_REF:0000033 | ACCEPT | Summary: FANCM functions in interstrand cross-link (ICL) repair; it is recruited to forks stalled by ICLs and is required for cellular resistance to cross-linking agents. This is a core biological process for FANCM, consistent across the phylogenetic tree (Hef/Mph1/Fml1). Reason: Well supported by both the phylogenetic inference and direct human experiments; ICL repair is a defining FANCM function. Supporting Evidence: PMID:20347428 FANCM and MHF are rapidly recruited to forks stalled by DNA interstrand crosslinks, and both are required for cellular resistance to such lesions. |
| GO:0000400 four-way junction DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: FANCM binds branched DNA including Holliday (four-way) junctions, which it processes by branch migration. Binding to four-way junction DNA is a conserved biochemical property. Reason: Supported by biochemistry showing FANCM processes Holliday junctions by branch migration, which requires four-way junction binding. Supporting Evidence: PMID:20347429 FANCM translocates on dsDNA and can unwind the D-loop and also process branched DNA structures, such as model DNA replication forks and the Holliday junction, by DNA branch migration PMID:18206976 purified FANCM binds to Holliday junctions and replication forks with high specificity and promotes migration of their junction point in an ATPase-dependent manner |
| GO:0009378 four-way junction helicase activity | IBA GO_REF:0000033 | ACCEPT | Summary: FANCM catalyzes ATP-dependent branch migration of Holliday (four-way) junctions, the activity captured by this term (Holliday junction branch migration/helicase activity), conserved from yeast Mph1/Fml1. Reason: FANCM demonstrably processes Holliday junctions by ATP-dependent branch migration; this term is an accurate description of that activity. Supporting Evidence: PMID:20347429 FANCM translocates on dsDNA and can unwind the D-loop and also process branched DNA structures, such as model DNA replication forks and the Holliday junction, by DNA branch migration PMID:18206976 FANCM can dissociate large recombination intermediates, via branch migration of Holliday junctions through 2.6 kb of DNA |
| GO:0043138 3'-5' DNA helicase activity | IBA GO_REF:0000033 | MODIFY | Summary: Human FANCM does not display canonical processive 3'-5' duplex-unwinding helicase activity; the characterized enzymatic activity is ATP-dependent DNA translocation and branch migration of branched substrates. The 3'-5' DNA helicase term (propagated from the SF2 family) is more accurately expressed as DNA translocase activity. Reason: Direct biochemistry states that for FANCM only translocase (not helicase) activity was observed; the branch-migration/fork-remodeling activity is best described as DNA translocase activity rather than a duplex-unwinding 3'-5' helicase. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000361481 · FANCM/Mph1/Fml1 family node SGD:S000001441 · MPH1 PomBase:SPAC9.05 · fml1 Proposed replacements: DNA translocase activity Supporting Evidence: PMID:19423727 for FANCM only translocase activity was observed |
| GO:0045003 double-strand break repair via synthesis-dependent strand annealing | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Yeast orthologs (Mph1/Fml1) promote synthesis-dependent strand annealing / gene conversion at blocked forks and channel recombination toward non-crossover outcomes. Human FANCM has a regulatory rather than essential role in this HR sub-pathway. Reason: SDSA is a conserved role of the FANCM clade but is regulatory/context-specific for human FANCM, which is not essential for RAD51-dependent HR; retain as a non-core process. Supporting Evidence: PMID:19423727 FANCM may have a more regulatory function in the homologous recombination process |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | ACCEPT | Summary: Broad InterPro-based binding term. FANCM binds DNA (more specific terms DNA binding and chromatin binding are separately annotated). Reason: Correct but general IEA parent of the more informative DNA-binding annotations; acceptable as a broad electronic annotation. |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: FANCM binds DNA, including single-stranded, fork-structured and branched substrates (and, with FAAP24/MHF, additional structures). Well supported. Reason: DNA binding is directly demonstrated and central to FANCM function. Supporting Evidence: PMID:20347429 FANCM translocates on dsDNA and can unwind the D-loop and also process branched DNA structures, such as model DNA replication forks and the Holliday junction, by DNA branch migration |
| GO:0003724 RNA helicase activity | IEA GO_REF:0000003 | REMOVE | Summary: This annotation derives from an EC:3.6.4.13 -> GO mapping and the legacy alternative name "ATP-dependent RNA helicase FANCM". Functionally FANCM is a DNA-dependent ATPase / DNA translocase; no RNA helicase activity has been demonstrated. Its measured catalytic reaction is simply ATP hydrolysis, and its substrates are DNA structures. Reason: Demonstrably incorrect EC-based electronic mapping: FANCM acts on DNA (translocase/branch migration), not RNA. The EC 3.6.4.13 assignment reflects ATP hydrolase activity, not genuine RNA helicase function. Supporting Evidence: PMID:19423727 for FANCM only translocase activity was observed |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: FANCM contains a Walker A/DEAH ATP-binding motif (residues 111-118, catalytic Lys117) and binds ATP, which it hydrolyzes to power DNA translocation. Reason: Directly supported by the conserved ATP-binding motif and ATPase mutagenesis (K117R). |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: FANCM is a nuclear protein. Well supported by multiple experimental studies. Reason: Consistent nuclear localization across studies. |
| GO:0006281 DNA repair | IEA GO_REF:0000120 | ACCEPT | Summary: FANCM functions broadly in DNA repair (ICL repair, replication fork protection, FA pathway activation). Correct general BP annotation. Reason: Accurate broad process term supported by the entire FANCM literature. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000116 | ACCEPT | Summary: FANCM is a DNA-dependent ATPase; ATP hydrolysis powers its translocase/branch-migration activity. Matches EC 3.6.4.13 (ATP + H2O -> ADP + Pi). Reason: Directly demonstrated DNA-stimulated ATPase activity; consistent with Rhea mapping. |
| GO:0035825 homologous recombination | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: FANCM regulates homologous recombination (D-loop disruption, fork reversal, suppression of crossovers/sister-chromatid exchange) but is not essential for RAD51-dependent HR repair itself. Reason: A genuine but regulatory HR role; patient cells with FANCM loss retain normal RAD51 foci, indicating FANCM is not a core HR enzyme. Retain as non-core. Supporting Evidence: PMID:19423727 normal Rad51 foci, indicating that FANCM is not essential for homologous recombination repair |
| GO:0043138 3'-5' DNA helicase activity | IEA GO_REF:0000002 | MODIFY | Summary: Duplicate of the IBA 3'-5' DNA helicase annotation, here from InterPro. As above, human FANCM's catalytic activity is ATP-dependent DNA translocation/branch migration rather than a processive duplex-unwinding helicase. Reason: Same rationale as the IBA entry: the SF2-family helicase mapping over-specifies FANCM's activity; DNA translocase activity is the accurate molecular function. Proposed replacements: DNA translocase activity Supporting Evidence: PMID:19423727 for FANCM only translocase activity was observed |
| GO:0005515 protein binding | IPI PMID:17289582 Identification of FAAP24, a Fanconi anemia core complex prot... | MARK AS OVER ANNOTATED | Summary: IPI capturing the FANCM-FAAP24 interaction. FAAP24 binds the C-terminal ERCC4-like region of FANCM and targets it to damaged-DNA structures. The interaction is biologically meaningful but the generic "protein binding" term is uninformative and is captured functionally by the FA core/complex annotations. Reason: "protein binding" (GO:0005515) is uninformative as a molecular function; the specific FANCM-FAAP24 interaction is represented via complex-membership terms. Supporting Evidence: PMID:17289582 associates with the C-terminal region of FANCM, and is a component of the FA core complex |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: High-throughput interactome mapping (interaction reported with TRIM27). Generic protein-binding annotation with no specific functional content. Reason: Uninformative "protein binding" term from a proteome-scale interactome screen. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: High-throughput binary interactome map (interaction reported with EPN2 isoform). Generic protein-binding annotation. Reason: Uninformative "protein binding" term from a large-scale interactome dataset. |
| GO:0005515 protein binding | IPI PMID:32769987 DONSON and FANCM associate with different replisomes disting... | MARK AS OVER ANNOTATED | Summary: Interaction with MCM2 reported in a replisome study; FANCM associates with a subset of replisomes in late-replicating heterochromatin. The generic protein-binding term does not convey this. Reason: Uninformative "protein binding" molecular-function term; replisome association is a process/localization observation, not a molecular function. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: High-throughput interactome (FAAP24 interaction). Duplicative generic protein-binding annotation. Reason: Uninformative "protein binding" term; the FANCM-FAAP24 relationship is captured by complex-membership annotations. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: Multimodal cell-map interactome (FAAP24 interaction). Generic protein-binding annotation. Reason: Uninformative "protein binding" term from a proteome-scale mapping effort. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence-based nucleoplasm localization (HPA). Consistent with FANCM being a nuclear, chromatin-associated protein. Reason: Consistent with the nuclear/chromatin localization of FANCM. |
| GO:0005634 nucleus | EXP PMID:16116422 A human ortholog of archaeal DNA repair protein Hef is defec... | ACCEPT | Summary: Experimentally determined nuclear localization of FANCM. Reason: Direct experimental evidence for nuclear localization. |
| GO:0005634 nucleus | EXP PMID:20347428 A histone-fold complex and FANCM form a conserved DNA-remode... | ACCEPT | Summary: Experimentally determined nuclear localization of FANCM (FANCM-MHF study). Reason: Direct experimental evidence for nuclear localization. |
| GO:0005634 nucleus | EXP PMID:20347429 MHF1-MHF2, a histone-fold-containing protein complex, partic... | ACCEPT | Summary: Experimentally determined nuclear localization; FANCM is in fact restricted to the chromatin fraction under all conditions tested. Reason: Direct experimental evidence for nuclear (chromatin) localization. Supporting Evidence: PMID:20347429 FANCM was exclusively detected in the chromatin (P; pellet) fraction under all conditions |
| GO:0005634 nucleus | EXP PMID:29231814 A homozygous FANCM mutation underlies a familial case of non... | ACCEPT | Summary: Nuclear localization of FANCM observed in germ cells (oogonia/oocytes). Reason: Direct experimental evidence for nuclear localization. Supporting Evidence: PMID:29231814 FANCM protein was preferentially expressed along the chromosomes in pachytene cells, which undergo meiotic recombination. |
| GO:0016887 ATP hydrolysis activity | EXP PMID:16116422 A human ortholog of archaeal DNA repair protein Hef is defec... | ACCEPT | Summary: Experimentally demonstrated ATPase activity of FANCM (mutagenesis of the ATP-binding motif abolishes it), underlying its DNA translocation. Reason: Direct experimental evidence; ATPase activity is a core catalytic property. Supporting Evidence: PMID:16116422 FANCM may act as an engine that translocates the FA core complex along DNA. |
| GO:0016887 ATP hydrolysis activity | EXP PMID:17289582 Identification of FAAP24, a Fanconi anemia core complex prot... | ACCEPT | Summary: Experimentally demonstrated ATPase activity of FANCM. Reason: Direct experimental evidence for the core DNA-dependent ATPase activity. |
| GO:0016887 ATP hydrolysis activity | EXP PMID:19423727 Impaired FANCD2 monoubiquitination and hypersensitivity to c... | ACCEPT | Summary: ATPase activity of FANCM demonstrated; required for cross-linker resistance (fork remodeling) but dispensable for FANCD2 monoubiquitination. Reason: Direct experimental evidence; the ATPase powers the translocase/remodeling function. Supporting Evidence: PMID:19423727 The ATPase activity of FANCM is required for cross-linker resistance but not for FANCD2 monoubiquitination and focus formation. |
| GO:0016887 ATP hydrolysis activity | EXP PMID:20347429 MHF1-MHF2, a histone-fold-containing protein complex, partic... | ACCEPT | Summary: ATP-dependent DNA branch migration by FANCM is abolished in the ATPase-dead K117R mutant, demonstrating the DNA-dependent ATPase activity. Reason: Direct experimental evidence linking ATP hydrolysis to FANCM branch-migration activity. Supporting Evidence: PMID:20347429 the ATPase deficient FANCMK117R mutant did not display any DNA branch migration activity even with MHF1-MHF2 present |
| GO:0000785 chromatin | IDA PMID:20347429 MHF1-MHF2, a histone-fold-containing protein complex, partic... | ACCEPT | Summary: FANCM is a chromatin-associated protein, detected exclusively in the chromatin fraction; it is where FANCM performs fork remodeling and anchors the FA core complex. Reason: Direct experimental evidence for chromatin localization. Supporting Evidence: PMID:20347429 FANCM was exclusively detected in the chromatin (P; pellet) fraction under all conditions |
| GO:0036297 interstrand cross-link repair | IDA PMID:20347429 MHF1-MHF2, a histone-fold-containing protein complex, partic... | ACCEPT | Summary: FANCM (via the MHF complex) functions in ICL repair and recovery of forks stalled by DNA-lesion/topoisomerase intermediates. Core biological process. Reason: Direct experimental evidence; ICL repair is a defining FANCM function. Supporting Evidence: PMID:20347429 MHF1 plays a role in ICL repair and in the recovery of replication forks stalled by topoisomerase I-DNA cleavage intermediates PMID:24207054 The traverse frequency was strongly reduced by inactivation of the translocase and DNA binding activities of the FANCM/MHF complex |
| GO:0071821 FANCM-MHF complex | IPI PMID:20347429 MHF1-MHF2, a histone-fold-containing protein complex, partic... | ACCEPT | Summary: FANCM forms a discrete complex with the MHF1-MHF2 (CENPS-CENPX) histone-fold heterodimer; MHF stimulates FANCM DNA binding and branch migration. FANCM is a core subunit of this complex. Reason: Direct evidence for FANCM-MHF complex membership. Supporting Evidence: PMID:20347429 MHF1 has also been identified as a component of the CENPA-CAD complex and named centromere protein S (CENPS) |
| GO:1902527 positive regulation of protein monoubiquitination | IMP PMID:29231814 A homozygous FANCM mutation underlies a familial case of non... | ACCEPT | Summary: FANCM is required for efficient DNA damage-induced monoubiquitination of FANCD2; patient cells with a truncating FANCM mutation show impaired MMC-induced FANCD2 monoubiquitination that is rescued by wild-type FANCM. This captures FANCM's positive regulation of FANCD2 (protein) monoubiquitination. Reason: Directly supported by loss-of-function and complementation experiments; a core signaling function of FANCM in the FA pathway. Supporting Evidence: PMID:29231814 improved their resistance to MMC re-establishing FANCD2 monoubiquitination |
| GO:0000077 DNA damage checkpoint signaling | IMP PMID:18995830 FANCM and FAAP24 function in ATR-mediated checkpoint signali... | NEW | Summary: FANCM (with FAAP24) is required for ATR/Chk1-mediated checkpoint signaling in response to replication stress, independently of the FA core complex: it interacts with the checkpoint protein HCLK2, and its DNA translocase activity (dispensable for FANCD2 monoubiquitination) is required for efficient Chk1 activation and downstream checkpoint responses. This checkpoint role is well documented (also via RPA and TopBP1 chromatin retention) but was not annotated in GOA. Reason: A genuine, well-evidenced function of FANCM that the existing GOA annotation set omits. Loss-of-function experiments show FANCM/FAAP24 depletion compromises ATR/Chk1 checkpoint signaling, and the translocase-dependence separates this activity from the scaffolding role in FANCD2 monoubiquitination. GO:0000077 (DNA damage checkpoint signaling) is a correctly-branched biological_process term for this role. Supporting Evidence: PMID:18995830 the DNA translocase activity of FANCM, which is dispensable for FA pathway activation, is required for its role in ATR/Chk1 signaling PMID:18995830 downregulation of FANCM or FAAP24 also compromises ATR/Chk1-mediated checkpoint signaling |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835411 | MARK AS OVER ANNOTATED | Summary: Cytosol localization derives from a Reactome PKR-signaling reaction (FA core complex:HSP70s binds PKR). FANCM is overwhelmingly nuclear and chromatin-restricted; a cytosolic pool is not a characteristic localization for its DNA-repair function. Reason: Peripheral pathway-derived localization inconsistent with the well-established nuclear/chromatin residence of FANCM; not a core location. Supporting Evidence: PMID:20347429 FANCM was exclusively detected in the chromatin (P; pellet) fraction under all conditions |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785361 | ACCEPT | Summary: Nucleoplasm localization from Reactome FA pathway reactions; consistent with FANCM's nuclear residence. Reason: Consistent with nuclear/chromatin localization; acceptable pathway-based CC annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785732 | ACCEPT | Summary: Nucleoplasm localization from Reactome FA pathway reactions. Reason: Consistent with nuclear localization of FANCM. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785986 | ACCEPT | Summary: Nucleoplasm localization from Reactome FA pathway reactions. Reason: Consistent with nuclear localization of FANCM. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6786166 | ACCEPT | Summary: Nucleoplasm localization from Reactome FA pathway reactions. Reason: Consistent with nuclear localization of FANCM. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6786171 | ACCEPT | Summary: Nucleoplasm localization from Reactome FA pathway reactions. Reason: Consistent with nuclear localization of FANCM. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6788392 | ACCEPT | Summary: Nucleoplasm localization from Reactome FA pathway reactions (ATR phosphorylation of FA proteins). Reason: Consistent with nuclear localization of FANCM. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785087 | ACCEPT | Summary: Nucleoplasm localization from Reactome FA pathway reactions (FANCM:FAAP24 binds ICL-DNA). Reason: Consistent with nuclear localization of FANCM. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785126 | ACCEPT | Summary: Nucleoplasm localization from Reactome FA pathway reactions (FA core complex assembly at ICLs). Reason: Consistent with nuclear localization of FANCM. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785342 | ACCEPT | Summary: Nucleoplasm localization from Reactome FA pathway reactions. Reason: Consistent with nuclear localization of FANCM. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785607 | ACCEPT | Summary: Nucleoplasm localization from Reactome FA pathway reactions (FANCM binds FAAP24). Reason: Consistent with nuclear localization of FANCM. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6786155 | ACCEPT | Summary: Nucleoplasm localization from Reactome FA pathway reactions. Reason: Consistent with nuclear localization of FANCM. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6788385 | ACCEPT | Summary: Nucleoplasm localization from Reactome FA pathway reactions (ATR:ATRIP recruitment to ICL-DNA). Reason: Consistent with nuclear localization of FANCM. |
| GO:0000712 resolution of meiotic recombination intermediates | IMP PMID:20347428 A histone-fold complex and FANCM form a conserved DNA-remode... | KEEP AS NON CORE | Summary: FANCM regulates recombination outcomes by processing/branch-migrating recombination intermediates and suppressing crossovers; in germ cells it is expressed along pachytene chromosomes. Consistent with a meiotic recombination-intermediate resolution role, though for human FANCM this is a tissue-specific/secondary function relative to its replication-fork role. Reason: Experimental (IMP) annotation by the curator; FANCM's anti-crossover/recombination-intermediate processing activity supports a meiotic role, but it is non-core relative to ICL repair and fork remodeling. Not removed, per deference to the experimental annotation. Supporting Evidence: PMID:29231814 FANCM protein was preferentially expressed along the chromosomes in pachytene cells, which undergo meiotic recombination. |
| GO:0031297 replication fork processing | IMP PMID:20347428 A histone-fold complex and FANCM form a conserved DNA-remode... | ACCEPT | Summary: FANCM remodels branched DNA structures and protects/processes stalled replication forks; MHF stimulates FANCM's replication fork remodeling. A core FANCM biological process. Reason: Directly supported experimental annotation; fork remodeling/processing is a central FANCM function driven by its translocase activity. Supporting Evidence: PMID:20347428 MHF stimulates DNA binding and replication fork remodeling by FANCM. |
| GO:0043240 Fanconi anaemia nuclear complex | IDA PMID:20347428 A histone-fold complex and FANCM form a conserved DNA-remode... | ACCEPT | Summary: FANCM is a component of the Fanconi anemia nuclear core complex (with FANCA/B/C/E/F/G/L, FAAP24, FAAP100, CENPS/CENPX), which it anchors to chromatin. Core complex membership. Reason: Direct experimental evidence for FA core complex membership. Supporting Evidence: PMID:20347428 FANCM-MHF associates with the Fanconi anemia (FA) core complex, promotes FANCD2 monoubiquitination in response to DNA damage, and suppresses sister-chromatid exchanges. |
| GO:0071821 FANCM-MHF complex | IDA PMID:20347428 A histone-fold complex and FANCM form a conserved DNA-remode... | ACCEPT | Summary: FANCM forms the FANCM-MHF complex with the CENPS-CENPX histone-fold dimer; this complex stimulates DNA binding and fork remodeling by FANCM. Reason: Direct experimental evidence for FANCM-MHF complex membership. Supporting Evidence: PMID:20347428 MHF stimulates DNA binding and replication fork remodeling by FANCM. |
| GO:0003682 chromatin binding | IDA PMID:20347429 MHF1-MHF2, a histone-fold-containing protein complex, partic... | ACCEPT | Summary: FANCM binds chromatin and is required for chromatin association of the FA core complex; it is detected exclusively in the chromatin fraction. Chromatin binding is central to its scaffolding/recruitment role. Reason: Direct experimental evidence; chromatin binding underlies FANCM's anchoring function. Supporting Evidence: PMID:20347429 FANCM was exclusively detected in the chromatin (P; pellet) fraction under all conditions |
| GO:0005515 protein binding | IPI PMID:20347429 MHF1-MHF2, a histone-fold-containing protein complex, partic... | MARK AS OVER ANNOTATED | Summary: IPI capturing the FANCM-CENPS (MHF1) interaction. Biologically meaningful (FANCM-MHF complex) but the generic "protein binding" term is uninformative and represented by the complex terms. Reason: "protein binding" (GO:0005515) is uninformative; the specific FANCM-CENPS/MHF interaction is captured by the FANCM-MHF complex annotation. Supporting Evidence: PMID:20347429 MHF1 has also been identified as a component of the CENPA-CAD complex and named centromere protein S (CENPS) |
| GO:0043240 Fanconi anaemia nuclear complex | IDA PMID:20347429 MHF1-MHF2, a histone-fold-containing protein complex, partic... | ACCEPT | Summary: FANCM is a component of the FA nuclear core complex; MHF1/MHF2 are identified as novel components of this complex via FANCM. Reason: Direct experimental evidence for FA core complex membership. Supporting Evidence: PMID:20347429 These results thus identify MHF1 and MHF2 as novel components of the FA core complex. |
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Download this section (compressed HTML)Q: Is the ATP-dependent DNA translocase/branch-migration activity of human FANCM required for replication traverse of ICLs and fork reversal in vivo, as distinct from its (ATPase-independent) scaffolding role in FANCD2 monoubiquitination?
Q: What is the direct in vivo substrate spectrum of the FANCM-MHF-FAAP24 assembly at stalled forks (regressed forks, D-loops, Holliday junctions), and how is activity partitioned between fork remodeling and checkpoint signaling?
Experiment: Separation-of-function analysis in FANCM-null human cells comparing wild-type, ATPase-dead (K117R), C-terminal (FAAP24-binding) deletion, and MHF-binding mutants for ICL traverse, fork reversal, FANCD2 monoubiquitination, ATR signaling, and SCE/crossover suppression.
Experiment: Single-molecule or reconstituted-fork biochemistry with purified FANCM +/- MHF1-MHF2 and FAAP24 to quantify translocation processivity and branch-migration directionality on defined fork/HJ substrates.
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