TP53BP1 (53BP1) - the end-protection factor that decides between the two repair routes, reachable only under the wrong symbol

{
  "tp53bp1_count": 0,
  "53bp1_count": 5,
  "on_beat_after_title_check": 3,
  "date": "2026-09-20",
  "lesson": "for a gene whose common name is a number-bearing abbreviation, the HGNC symbol returns a clean zero"
}

{
  "chronos_mean_kmt2a_rearranged": -0.1954,
  "chronos_mean_other_leukaemia": -0.1934,
  "difference": -0.002,
  "pan_essentiality_all_lines": -0.0642,
  "selectivity_rank": 8906,
  "rank_denominator": 17728,
  "provenance": "Joined 2026-09-21 from analyses/depmap-kmt2a-selective-scan-full (generated 2026-09-19T10:12:06Z), the project's own genome-wide scan over 11 KMT2A-rearranged and 43 other leukaemia DepMap lines. NOT re-fetched and NOT independent of that scan: every caveat it carries applies here, including that the KMT2A-rearranged arm is a small number of lines drawn from nine individuals, that the rank denominator is 17,728 genes, and that a difference is not a dependency. Added because only 26 of 308 gene entries carried this number, which made any KMT2A-selectivity question answerable for 8% of the corpus.",
  "how_to_read": "A negative difference means MORE required in KMT2A-rearranged lines than in other leukaemia lines. A rank near 17,728 is ANTI-selective. Neither is evidence of a fusion-driven dependency on its own: check pan_essentiality_all_lines before calling anything selective, and note that a paralogue-redundant gene can score near zero for reasons that have nothing to do with this disease - see ana-the-paralogue-redundancy-excuse-is-not-tested-and-my-proxy-decided-the-answer."
}

{
  "CONSTITUTIVE": "NUCLEOPLASMIC AND DIFFUSE, AND UNIPROT SAYS SO IN THOSE WORDS. Q12888 fetched 2026-09-21 carries 'Nucleus' on nine ECO:0000269 attributions and 'Chromosome' on nine more, and its note opens: 'Localizes to the nucleus in ABSENCE OF DNA DAMAGE (PubMed:28241136).' That sentence is the constitutive record and it is unusually explicit - most proteins in this tranche have no resting-state statement at all [E_q89_tp53bp1_loc1].",
  "INDUCED": "IONISING-RADIATION-INDUCED FOCI AT DOUBLE-STRAND BREAKS, and the recruitment is READER-DRIVEN: following DNA damage 53BP1 is recruited to sites of damage where it recognises and binds histone H2A monoubiquitinated at Lys-15 (H2AK15Ub) and histone H4 dimethylated at Lys-20 (H4K20me2), the two marks present at DSB sites. UniProt cites seven ECO:0000269 papers for this [E_q89_tp53bp1_loc1].",
  "A_THIRD_STATE_THAT_IS_NEITHER": "53BP1 NUCLEAR BODIES IN G1, which are not resting distribution and not an acute damage response. Mild replication stress increases the frequency of chromosomal lesions TRANSMITTED THROUGH MITOSIS to daughter cells; throughout G1 those inherited lesions are sequestered in nuclear compartments marked by 53BP1 and other chromatin-associated genome caretakers. Ablating the BLM helicase increases these bodies; knocking down the condensin subunit SMC2 partially suppresses them; and the bodies SHIELD chromosomal fragile sites against erosion [E_q89_tp53bp1_loc2].",
  "why_three_states_and_not_one": "A single resting-state answer would be wrong, as it is for PARP1 in this same tranche. Diffuse nucleoplasmic, IRIF at breaks, and G1 nuclear bodies around inherited under-replicated lesions are three different distributions with three different triggers, and only the first is what an unperturbed cell shows."
}

{
  "in_this_disease": "UMBILICAL-CORD-BLOOD MONONUCLEAR CELLS AND MLL-REARRANGED AML LINES, and in both the protein is an INSTRUMENT rather than a subject - which this entry already says about the literature generally. Cord blood positive for AML preleukaemic fusion genes including KMT2A-MLLT3 accumulated the same level of endogenous DNA damage as fusion-negative cord blood, scored by 53BP1 together with gamma-H2AX foci (this entry's existing E2). In Molm-13 and MV4-11, chidamide plus (+)-JQ-1 reduced 53BP1 protein and mRNA alongside RAD51 (E3).",
  "the_cell_type_the_foci_were_counted_in": "Backtracked umbilical cord blood of children who later developed acute leukaemia [E_q89_tp53bp1_loc3] - a genuinely unusual and valuable cell type, because it is a normal neonatal haematopoietic population sampled before disease.",
  "not_measured": "No 53BP1 localisation experiment exists in a KMT2A-rearranged blast. Foci COUNTS exist; a compartment measurement does not, and the two are not the same - counting foci presupposes the induced state and cannot describe the resting one."
}

{
  "CELL_CYCLE": "The dominant state variable. 53BP1 nuclear bodies are a G1 phenomenon by definition, formed around lesions inherited through the preceding mitosis [E_q89_tp53bp1_loc2]; the kinetochore association, such as it is, is mitotic and inferred from mouse [E_q89_tp53bp1_loc1]. So 'where is 53BP1' cannot be answered without naming the phase.",
  "REPLICATION_STRESS": "The state that generates the bodies. See cell-state-replication-stress-icl-repair. Mild replication stress is sufficient - no exogenous break-inducing agent is needed - which is why this is a cell state rather than a treatment.",
  "PATHWAY_CHOICE": "53BP1's function is to bias repair toward NHEJ by protecting ends from resection, and this entry already argues that pathway choice determines the junction signature at KMT2A breakpoints. The localisation record adds the constraint that the protein has to BE at the end for that choice to be made, and the reader marks that recruit it (H2AK15Ub, H4K20me2) are themselves chromatin-state-dependent."
}

{
  "date": "2026-09-21",
  "tool": "NCBI esearch db=pubmed",
  "queries": [
    {
      "query": "53BP1[tiab] AND (\"nuclear bodies\"[tiab] OR \"nuclear body\"[tiab])",
      "querytranslation": "\"53BP1\"[Title/Abstract] AND (\"nuclear bodies\"[Title/Abstract] OR \"nuclear body\"[Title/Abstract])",
      "count": 55
    },
    {
      "query": "53BP1[ti] AND \"nuclear bodies\"[ti]",
      "querytranslation": "\"53BP1\"[Title] AND \"nuclear bodies\"[Title]",
      "count": 5,
      "ids": [
        "33141022",
        "31009828",
        "30804506",
        "29206178",
        "21317883"
      ]
    }
  ],
  "reading": "A 55-record nuclear-body literature and a five-record core of papers titled for it, and none of them is in a KMT2A-rearranged or MLL-rearranged cell. This entry's existing E4 records the symbol trap that governs all retrieval here - (MLL OR KMT2A) AND TP53BP1 returns 0 while (MLL OR KMT2A) AND 53BP1 returns 5 - so every bound on this gene must be run under the nickname, not the HGNC symbol.",
  "absence_class": "never-measured"
}