We will use two model systems to study DNA replication in human cell lines. 1. The role of the Epstein-Barr virus (EBV) nuclear antigen I (EBNA-1) in the formation of a replication barrier at the EBV family of repeated sequences in human cell lines will be studied using an in vitro replication system. We will determine the minimum number of repeats that are required to produce a barrier to replication in vitro and determine whether EBNA-1 binding to the family of repeats inhibits helicase activity of the T antigen. We will then determine whether cellular proteins can also produce a replication barrier by binding to the EBV family of repeats. 2. We will identify replication origins in the rDNA gene cluster that replicate early or late during the S phase. We will determine the location of the sites at which the replication of the immunoglobulin heavy chain multigene family initiates. This will be determined in cell lines in which one or more of these genes are expressed and in cell lines in which they are transcriptionally silent. We will use deletion analysis to determine the sequences that are critical for these immunoglobulin replication origins to function. Targeted integration mediated by homologous recombination will be used to modify the chromosomal origin region.
| Pan, Xiaolei; Drosopoulos, William C; Sethi, Louisa et al. (2017) FANCM, BRCA1, and BLM cooperatively resolve the replication stress at the ALT telomeres. Proc Natl Acad Sci U S A 114:E5940-E5949 |
| Madireddy, Advaitha; Purushothaman, Pravinkumar; Loosbroock, Christopher P et al. (2016) G-quadruplex-interacting compounds alter latent DNA replication and episomal persistence of KSHV. Nucleic Acids Res 44:3675-94 |
| Madireddy, Advaitha; Kosiyatrakul, Settapong T; Boisvert, Rebecca A et al. (2016) FANCD2 Facilitates Replication through Common Fragile Sites. Mol Cell 64:388-404 |
| Calderano, Simone Guedes; Drosopoulos, William C; Quaresma, Marina Mônaco et al. (2015) Single molecule analysis of Trypanosoma brucei DNA replication dynamics. Nucleic Acids Res 43:2655-65 |
| Drosopoulos, William C; Kosiyatrakul, Settapong T; Schildkraut, Carl L (2015) BLM helicase facilitates telomere replication during leading strand synthesis of telomeres. J Cell Biol 210:191-208 |
| Gerhardt, Jeannine; Zaninovic, Nikica; Zhan, Qiansheng et al. (2014) Cis-acting DNA sequence at a replication origin promotes repeat expansion to fragile X full mutation. J Cell Biol 206:599-607 |
| Gerhardt, Jeannine; Tomishima, Mark J; Zaninovic, Nikica et al. (2014) The DNA replication program is altered at the FMR1 locus in fragile X embryonic stem cells. Mol Cell 53:19-31 |
| Murphy, Anar K; Fitzgerald, Michael; Ro, Teresa et al. (2014) Phosphorylated RPA recruits PALB2 to stalled DNA replication forks to facilitate fork recovery. J Cell Biol 206:493-507 |
| Jeong, Yeon-Tae; Rossi, Mario; Cermak, Lukas et al. (2013) FBH1 promotes DNA double-strand breakage and apoptosis in response to DNA replication stress. J Cell Biol 200:141-9 |
| Drosopoulos, William C; Kosiyatrakul, Settapong T; Yan, Zi et al. (2012) Human telomeres replicate using chromosome-specific, rather than universal, replication programs. J Cell Biol 197:253-66 |
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