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Furthermore, using the cell cycle system as an example, we show through a combination of theory and experiments that such \u201cregulatory modules\u201d actually exist in living organisms, performing important roles. In the cell cycle, the G\n                    <jats:sub>1<\/jats:sub>\n                    -S and G\n                    <jats:sub>2<\/jats:sub>\n                    -M transitions are strictly controlled by distinct protein complexes, requiring the specific activation of different complexes at different phases. This suggests that different transitions should be independently controlled. However, two cell-cycle-control complexes share a common protein component, raising the question of how phase-specific control is achieved. Analysis of a known cell cycle network using a topology-based theory revealed that the two complexes belong to different regulatory modules. Experimental verification confirms the existence of a module. Moreover, by comparing theoretical predictions with experimental verification, we theoretically predict the necessity of an unknown reaction and experimentally confirm it. This prediction and verification approach using model-free theory enables the updating of the network information.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2537815123","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:25:03Z","timestamp":1790180703000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Network topology creates independent control of multiple checkpoints in the cell cycle system"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1162-5289","authenticated-orcid":false,"given":"Yuhei","family":"Yamauchi","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00pqz0q24","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Mathematical Biology, Institute for Life and Medical Sciences, Kyoto University","place":["Kyoto, 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