Mol._Cell._Biol.-2006-Ampatzidou-9387-401.pdf (904.92 kB)
Smc5/6 is required for repair at collapsed replication forks.
journal contributionposted on 2023-06-08, 07:31 authored by Eleni Ampatzidou, Anja Irmisch, Matthew J O'Connell, Jo Murray
In eukaryotes, three pairs of structural-maintenance-of-chromosome (SMC) proteins are found in conserved multisubunit protein complexes required for chromosomal organization. Cohesin, the Smc1/3 complex, mediates sister chromatid cohesion while two condensin complexes containing Smc2/4 facilitate chromosome condensation. Smc5/6 scaffolds an essential complex required for homologous recombination repair. We have examined the response of smc6 mutants to the inhibition of DNA replication. We define homologous recombination-dependent and -independent functions for Smc6 during replication inhibition and provide evidence for a Rad60-independent function within S phase, in addition to a Rad60-dependent function following S phase. Both genetic and physical data show that when forks collapse (i.e., are not stabilized by the Cds1Chk2 checkpoint), Smc6 is required for the effective repair of resulting lesions but not for the recruitment of recombination proteins. We further demonstrate that when the Rad60-dependent, post-S-phase Smc6 function is compromised, the resulting recombination-dependent DNA intermediates that accumulate following release from replication arrest are not recognized by the G2/M checkpoint.
- Published version
JournalMolecular and Cellular Biology
Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
NotesJM directed the research and was the corresponding author. Research 100% my lab. M O'C, New York, an author as part of a long-standing collaboration. First demonstration of a role for the essential structural-maintenance-of-chromosome Smc5/6 complex in the repair of collapsed replication forks.
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