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Dual Roles of Poly(dA:dT) Tracts in Replication Initiation and Fork Collapse
| Content Provider | Scilit |
|---|---|
| Author | Tubbs, Anthony Sridharan, Sriram van Wietmarschen, Niek Maman, Yaakov Callen, Elsa Stanlie, Andre Wu, Wei Wu, Xia Day, Amanda Wong, Nancy Yin, Mianmian Canela, Andres Fu, Haiqing Redon, Christophe Pruitt, Steven C. Jaszczyszyn, Yan Aladjem, Mirit I. Aplan, Peter D. Hyrien, Olivier Nussenzweig, André |
| Copyright Year | 2018 |
| Description | Journal: Cell Summary 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 (>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. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591735/pdf http://www.cell.com/article/S009286741830905X/pdf |
| ISSN | 00928674 |
| e-ISSN | 10974172 |
| DOI | 10.1016/j.cell.2018.07.011 |
| Journal | Cell |
| Issue Number | 5 |
| Volume Number | 174 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2018-08-02 |
| Access Restriction | Open |
| Subject Keyword | Journal: Cell Cell Biology Dna Breaks Replication Origins Fragile Sites Genome Instability Replication Stress Ribosomal Dna Replication Fork Barrier Poly(da:dt) Tracts |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry, Genetics and Molecular Biology |
