| RRC ID |
82777
|
| Author |
Szmyd R, Casolin S, French L, Manjón AG, Walter M, Cavalli L, Nelson CB, Page SG, Dhawan A, Hau E, Pickett HA, Gee HE, Cesare AJ.
|
| Title |
Homologous recombination promotes non-immunogenic mitotic cell death upon DNA damage.
|
| Journal |
Nat Cell Biol
|
| Abstract |
Double-strand breaks (DSBs) can initiate mitotic catastrophe, a complex oncosuppressive phenomenon characterized by cell death during or after cell division. Here we unveil how cell cycle-regulated DSB repair guides disparate cell death outcomes through single-cell analysis of extended live imaging. Following DSB induction in S or G2, passage of unresolved homologous recombination intermediates into mitosis promotes non-immunogenic intrinsic apoptosis in the immediate attempt at cell division. Conversely, non-homologous end joining, microhomology-mediated end joining and single-strand annealing cooperate to enable damaged G1 cells to complete the first cell cycle with an aberrant cell division at the cost of delayed extrinsic lethality and interferon production. Targeting non-homologous end joining, microhomology-mediated end joining or single-strand annealing promotes mitotic death, while suppressing mitotic death enhances interferon production. Together the data indicate that a temporal repair hierarchy, coupled with cumulative DSB load, serves as a reliable predictor of mitotic catastrophe outcomes following genome damage. In this pathway, homologous recombination suppresses interferon production by promoting mitotic lethality.
|
| Volume |
27(1)
|
| Pages |
59-72
|
| Published |
2025-1-1
|
| DOI |
10.1038/s41556-024-01557-x
|
| PII |
10.1038/s41556-024-01557-x
|
| PMID |
39805921
|
| PMC |
PMC11735404
|
| MeSH |
Animals
Apoptosis / genetics
Cell Death / genetics
DNA Breaks, Double-Stranded*
DNA Damage
DNA End-Joining Repair
DNA Repair
Homologous Recombination*
Humans
Interferons / genetics
Interferons / metabolism
Mice
Mitosis* / genetics
|
| IF |
20.042
|
| Resource |
| DNA material |
tFucci(CA)2/pCSII-EF (RDB15446) |
