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Barcelona BioMed Seminar: Dual Roles of Poly(dA:dT) Tracts in Replication Initiation and Fork Collapse

Descripció:

Replication origins, fragile sites, and rDNA have been implicated as sources of chromosomal instability. However, the defining genomic features of replication origins and fragile sites are among the least understood elements of eukaryote genomes. Here, we map sites of replication initiation and breakage in primary cells at high resolution. We find that replication initiates between transcribed genes within nucleosome-depleted structures established by long asymmetrical poly(dA:dT) tracts flanking the initiation site. Paradoxically, long (&gt;20 bp) (dA:dT) tracts are also preferential sites of polar replication fork stalling and collapse within early-replicating fragile sites (ERFSs) and late-replicating common fragile sites (CFSs) and at the rDNA replication fork barrier. Poly(dA:dT) sequences are fragile because long single-strand poly(dA) stretches at the replication fork are unprotected by the replication protein A (RPA). We propose that the evolutionary expansion of poly(dA:dT) tracts in eukaryotic genomes promotes replication initiation, but at the cost of chromosome fragility.

Oncology Programme Seminar

Data i hora d'inici: 04/10/2018, 12.00h

Data i hora de fi: 04/10/2018, 14.00h

Organitzador: IRB - Institut de Recerca Biomèdica

Lloc: Edifci Clúster Laboratoris, Aula Félix Serratosa

Host: Dr. Travis Stracker