Abstract

In the human beta globin locus, two sequences (one co-localizing to the initiation site and the other distal to it) are essential for initiating DNA replication. The beta globin initiation site acts as a genetic replicator and is the subject of a detailed structure-function analysis of the sequences required for initiation of DNA. During the last year we have narrowed down the sequences essential for initiation of DNA replication by analyzing several deletion mutants and are now modifying individual sequence elements that are common to replication origins to determine whether these sequences are required for initiation. We are also using the beta-globin locus as a model system to study how replication timing and origin usage are coordinated with gene expression patterns and correlated with local chromatin features. Finally, we are currently developing protocols for genomic hybridization on microarrays, a whole genome approaches to identify multiple replication origins.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010411-02
Application #
6559265
Study Section
(LMP)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2001
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Conti, Chiara; Leo, Elisabetta; Eichler, Gabriel S et al. (2010) Inhibition of histone deacetylase in cancer cells slows down replication forks, activates dormant origins, and induces DNA damage. Cancer Res 70:4470-80
Aladjem, Mirit; Chattoraj, Dhruba K (2009) EMBO Conference on Replication and Segregation of Chromosomes, Geilo, Norway, June 16-20. Replication and segregation of chromosomes in the three domains of life: EMBO conference reports common grounds. Meeting report. Plasmid 61:89-93
Seiler, Jennifer A; Conti, Chiara; Syed, Ali et al. (2007) The intra-S-phase checkpoint affects both DNA replication initiation and elongation: single-cell and -DNA fiber analyses. Mol Cell Biol 27:5806-18
Shimura, Tsutomu; Martin, Melvenia M; Torres, Michael J et al. (2007) DNA-PK is involved in repairing a transient surge of DNA breaks induced by deceleration of DNA replication. J Mol Biol 367:665-80
Fu, Haiqing; Wang, Lixin; Lin, Chii-Mei et al. (2006) Preventing gene silencing with human replicators. Nat Biotechnol 24:572-6
Feng, Yong-Qing; Desprat, Romain; Fu, Haiqing et al. (2006) DNA methylation supports intrinsic epigenetic memory in mammalian cells. PLoS Genet 2:e65
Wang, Lixin; Lin, Chii Mei; Lopreiato, Joseph O et al. (2006) Cooperative sequence modules determine replication initiation sites at the human beta-globin locus. Hum Mol Genet 15:2613-22
Wang, Jin; Liu, Hui; Lin, Chi Mei et al. (2005) Targeted deletion of the chicken beta-globin regulatory elements reveals a cooperative gene silencing activity. J Biol Chem 280:23340-8
Feng, Yong-Qing; Warin, Renaud; Li, Taihao et al. (2005) The human beta-globin locus control region can silence as well as activate gene expression. Mol Cell Biol 25:3864-74
Wang, Lixin; Lin, Chii-Mei; Brooks, Sarah et al. (2004) The human beta-globin replication initiation region consists of two modular independent replicators. Mol Cell Biol 24:3373-86

Showing the most recent 10 out of 14 publications