Abstract

The research in this lab is to study how eukaryotic cells maintain their genomes. Normal cells can faithfully transmit their genetic information. When cells lose this ability, as having been found in many human genetic diseases, secondary mutations would frequently arise. Most of these mutations will be deleterious to cells and cause early senescence. However, some mutations may activate oncogenes or inactive tumor suppressor genes and cancer will eventually evolve. The experiments proposed here are designed to use the frog egg extract as a model system to study the structure and function of FFA-1, a protein required for the organization of replication foci on chromatin. Specifically, FFA-1 will be depleted from egg extracts and the effect on DNA replication will be assessed. These studies will reveal novel information on how genomic stability is maintained, which may be used to for the design of new anti-cancer drugs and/or drugs that delay the aging process.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057962-02
Application #
6019461
Study Section
Genetics Study Section (GEN)
Project Start
1998-08-01
Project End
2003-07-31
Budget Start
1999-08-01
Budget End
2000-07-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Institute for Cancer Research
Department
Type
DUNS #
872612445
City
Philadelphia
State
PA
Country
United States
Zip Code
19111

  Publications

Liao, Shuren; Tammaro, Margaret; Yan, Hong (2016) The structure of ends determines the pathway choice and Mre11 nuclease dependency of DNA double-strand break repair. Nucleic Acids Res 44:5689-701
Yan, Hong; Tammaro, Margaret; Liao, Shuren (2016) Collision of Trapped Topoisomerase 2 with Transcription and Replication: Generation and Repair of DNA Double-Strand Breaks with 5' Adducts. Genes (Basel) 7:
Tammaro, Margaret; Liao, Shuren; Beeharry, Neil et al. (2016) DNA double-strand breaks with 5' adducts are efficiently channeled to the DNA2-mediated resection pathway. Nucleic Acids Res 44:221-31
Liao, Shuren; Tammaro, Margaret; Yan, Hong (2015) Enriching CRISPR-Cas9 targeted cells by co-targeting the HPRT gene. Nucleic Acids Res 43:e134
Arora, Sanjeevani; Yan, Hong; Cho, Iltaeg et al. (2015) Genetic Variants That Predispose to DNA Double-Strand Breaks in Lymphocytes From a Subset of Patients With Familial Colorectal Carcinomas. Gastroenterology 149:1872-1883.e9
Tammaro, Margaret; Liao, Shuren; McCane, Jill et al. (2015) The N-terminus of RPA large subunit and its spatial position are important for the 5'->3' resection of DNA double-strand breaks. Nucleic Acids Res 43:8790-800
Tammaro, Margaret; Barr, Peri; Ricci, Brett et al. (2013) Replication-dependent and transcription-dependent mechanisms of DNA double-strand break induction by the topoisomerase 2-targeting drug etoposide. PLoS One 8:e79202
Peterson, Shaun E; Li, Yinyin; Wu-Baer, Foon et al. (2013) Activation of DSB processing requires phosphorylation of CtIP by ATR. Mol Cell 49:657-67
Liao, Shuren; Guay, Catherine; Toczylowski, Thomas et al. (2012) Analysis of MRE11's function in the 5'-->3' processing of DNA double-strand breaks. Nucleic Acids Res 40:4496-506
Liao, Shuren; Toczylowski, Thomas; Yan, Hong (2011) Mechanistic analysis of Xenopus EXO1's function in 5'-strand resection at DNA double-strand breaks. Nucleic Acids Res 39:5967-77

Showing the most recent 10 out of 17 publications