This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.DNA double stranded breaks are often encountered within a cell as intermediates of particular recombination processes or can be induced by external agents such as ionizing radiation and radiomimetic drugs. In addition, double strand breaks can also occur as a result of the by-products released during metabolism. It is crucial to repair double strand breaks effectively and this is carried out by two distinct repair mechanisms, one of which is non-homologous end joining repair pathway. Although the other repair mechanism exists, NHEJ is predominant in higher eukaryotes and prevails all through out the cell cycle. Xrcc4-DNA ligase IV complex is an absolutely essential component of NHEJ pathway and is responsible for carrying out the final step of ligating the broken DNA ends. Solving the crystal structure of this human complex could provide us with great insights and revelations that could shed light on the actual mechanism of this pathway, which is currently unclear. Also, since the lack of proper double strand break repair causes apoptosis in a cell, developing inhibitors of this complex through structure-based drug design could provide a novel treatment for cancer that can be used in combination with radiation therapy.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR012408-11
Application #
7602315
Study Section
Special Emphasis Panel (ZRG1-PC (02))
Project Start
2007-07-01
Project End
2008-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
11
Fiscal Year
2007
Total Cost
$17,098
Indirect Cost
Name
Brookhaven National Laboratory
Department
Type
DUNS #
027579460
City
Upton
State
NY
Country
United States
Zip Code
11973
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