sad1 (S. pombe, Q09825) review notes

Context: reviewed as a fungal comparative member of modules/linc_complex.yaml (SUN component) and the
nucleokinesis module. Human comparators: SUN1, SUN2.

Biology (with provenance)

• Essential SUN protein; SPB-associated throughout mitosis and meiosis PMID:7744953.
• INM SUN protein pairing with KASH Kms1 to form a LINC PMID:30462301.
• Mitotic partner Kms2; Sad1-Kms2-Ima1 couple centromeric heterochromatin to microtubules PMID:18692466.
• Centromere clustering: Sad1 + Csi1 link centromeres to the INM near the SPB PMID:23166349; Sad1 residues 2-60 confer centromere-LINC association PMID:27889481.
• SPB insertion: Sad1 ring at mitotic entry, first in the ring-assembly order Sad1 > Kms2/Cut12 > Cut11 PMID:34133218; "mutation of sad1+ results in SPB insertion errors" PMID:28619713.
• Meiosis: Bqt1-Bqt2 bridge Rap1 to Sad1 PMID:16615890; bouquet linked to SPB via Sad1-Kms1 LINC PMID:27889481.
• DNA damage: Sad1-Kms1 foci at persistent DSBs, coupling to microtubules PMID:24943839; basis of GO:1990612.
• Histone H2A-H2B binding by an N-terminal HBM, crystal structure; peripheral heterochromatin tethering/silencing PMID:38773107.

Decisions

• Protein binding rows: Kms1 -> MODIFY GO:0140444 (consistent with human SUN reviews); Bqt1 and Csi1 -> MODIFY GO:0043495 (Sad1 as membrane anchor for telomere/centromere complexes); Sif1, Ufe1 (Y2H screen) and Bqt4 (in vitro peptide, in vivo untested) -> REMOVE as uninformative.
• GO:0034993 IPI with Kms2 -> MODIFY to GO:0106094 (Kms2 is the mitotic SPB KASH partner); IBA GO:0034993 accepted (Sad1-Kms1 is meiotic).
• GO:1990612 verified in QuickGO: "Sad1-Kms1 LINC complex", defined around DSB repair, is_a GO:0034993. Accepted; ontology question raised.
• NEW GO:0042393 histone binding (IDA, PMID:38773107).
• All localization rows accepted; iMTOC and site of DSB kept as non-core.

Deep research

sad1-deep-research-falcon.md read and incorporated (histone binding study, SPB ring model); led to adding PMID:38773107 and PMID:18692466.

Module implications

• Sad1 confirms the SUN component is deeply conserved: SUN-KASH anchor (GO:0140444), nucleoplasmic partner anchoring (telomeres, centromeres), and meiotic telomere clustering are shared with human SUN1.
• Fungal-specific: SPB anchoring/insertion into a closed-mitosis nuclear envelope (GO:0106166, GO:0140480) and centromere (Rabl) tethering; these are the fungal counterparts of centrosome-nucleus coupling.
• Single SUN protein partners with two KASH proteins in different contexts (Kms2 mitotic/SPB; Kms1 meiotic/DSB), mirroring the variant structure of the module's KASH component.