DNA replication checkpoint sensors
- Principle investigator:
- Neus Agell
- Contact details:
DNA replication checkpoint is essential to inhibit mitosis entry when DNA is not fully replicated. During the last 5 years we have demonstrated the existence of new cellular responses that lead to inhibition of mitosis entry in the presence of non-replicated DNA and which are therefore important to maintain genome integrity. We have also demonstrated that these response pathways are independent of ATR/Chk1 and, interestingly, they are functional in non-transformed cell lines, but not functional in the great majority of cancer cell lines analyzed.
Our purpose is to analyze the molecular mechanisms of these responses, with specific interest in the molecules associated to the chromatin that could be new the sensors of the DNA replication checkpoint.
The techniques to be used will be: General cell biology and molecular biology techniques; Analysis of chromatin associated proteins; Chromatin immunoprecipitation; Advanced optical microscopy techniques; FACS techniques; proteomics.
The project is a continuation of work published in Oncogene. 2003, 22:8283-92; Cancer Res. 2006, 66:8672-8679; and Cancer Res. 2007, 67:11648-56; Traffic. 2010 Jun;11(6):743-55.
DNA replication, Checkpoint, Chk1, ATR, claspin, SAPK
To conduct research investigating proteins associated to chromatin upon activation of the DNA replication checkpoint.
It is expected a thorough background on cell cycle regulatory mechanisms and chromatin remodeling mechanisms. In addition, it will be important to show ability to develop ideas logically and design experiments to test hypotheses, ability to modify and apply new methods to advance a project, and to analyze and write up data for presentations and publications.
Team strategic objective in IDIBAPS
The group of Dr. Neus Agell is included in the IDIBPAS team “cell proliferation and signaling”. Among the strategic objectives of this team the ones in which the group of Dr. N. Agell is involved are:
- A. Signaling and regulation of the cell cycle.
- B. Cell Cycle: signal transduction and checkpoints