Studies in Saccharomyces cerevisiae have identified homologous recombination as the major mechanism for repairing DNA double-strand breaks induced by ionizing radiation. During the repair process, the ends of the DNA breaks are processed nucleolytically to yield 3' ssDNA tails, which are bound by recombination factors. The nucleoprotein complex thus formed then conducts a search to locate an undamaged DNA homolog and catalyzes the formation of heteroduplex DNA with the homolog. The RAD5O, RAD5I, RAD52, RAD55, RAD57, RAD59, MRE11, and XRS2 genes are key members of the evolutionarily conserved RAD52 epistasis group that mediate mitotic and meiotic recombination and the recombinational repair of DNA double-strand breaks. The RAD5O, MRE11, and XRS2 encoded products are associated in a complex that plays a central role in double-strand break end-processing. Rad5l protein, with the aid of ancillary factors, nucleates onto the ssDNA tails to form a nucleoprotein filament that has the ability to initiate heteroduplex DNA formation. A combination of biochemical and genetic approaches will be used to (i) delineate the functions of Rad5O, Mre11, Xrs2, and the complex consisting of these proteins, (ii) identify protein factors that functionally and physically interact with the Rad50-Mrel l-Xrs2 complex in DNA end- processing, and (iii) dissect the mechanism of action of Rad5 l, Rad52, Rad55, Rad57, and Rad59 proteins in heteroduplex DNA formation. The results from these studies will be important for understanding the mechanism of DNA double-strand break re air b recombination in eukaryotes including humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
2R01ES007061-07A1
Application #
6196610
Study Section
Radiation Study Section (RAD)
Program Officer
Velazquez, Jose M
Project Start
1995-01-01
Project End
2005-06-30
Budget Start
2000-09-30
Budget End
2001-06-30
Support Year
7
Fiscal Year
2000
Total Cost
$314,000
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Crickard, J Brooks; Kaniecki, Kyle; Kwon, Youngho et al. (2018) Meiosis-specific recombinase Dmc1 is a potent inhibitor of the Srs2 antirecombinase. Proc Natl Acad Sci U S A 115:E10041-E10048
Rao, Timsi; Longerich, Simonne; Zhao, Weixing et al. (2018) Importance of homo-dimerization of Fanconi-associated nuclease 1 in DNA flap cleavage. DNA Repair (Amst) 64:53-58
Sung, Patrick (2018) Introduction to the Thematic Minireview Series: DNA double-strand break repair and pathway choice. J Biol Chem 293:10500-10501
Crickard, J Brooks; Kaniecki, Kyle; Kwon, YoungHo et al. (2018) Spontaneous self-segregation of Rad51 and Dmc1 DNA recombinases within mixed recombinase filaments. J Biol Chem 293:4191-4200
Crickard, J Brooks; Kaniecki, Kyle; Kwon, YoungHo et al. (2018) Regulation of Hed1 and Rad54 binding during maturation of the meiosis-specific presynaptic complex. EMBO J 37:
Wang, Weibin; Daley, James M; Kwon, Youngho et al. (2018) A DNA nick at Ku-blocked double-strand break ends serves as an entry site for exonuclease 1 (Exo1) or Sgs1-Dna2 in long-range DNA end resection. J Biol Chem 293:17061-17069
Kaniecki, Kyle; De Tullio, Luisina; Gibb, Bryan et al. (2017) Dissociation of Rad51 Presynaptic Complexes and Heteroduplex DNA Joints by Tandem Assemblies of Srs2. Cell Rep 21:3166-3177
Daley, James M; Jimenez-Sainz, Judit; Wang, Weibin et al. (2017) Enhancement of BLM-DNA2-Mediated Long-Range DNA End Resection by CtIP. Cell Rep 21:324-332
De Tullio, Luisina; Kaniecki, Kyle; Kwon, Youngho et al. (2017) Yeast Srs2 Helicase Promotes Redistribution of Single-Stranded DNA-Bound RPA and Rad52 in Homologous Recombination Regulation. Cell Rep 21:570-577
Miller, Adam S; Daley, James M; Pham, Nhung Tuyet et al. (2017) A novel role of the Dna2 translocase function in DNA break resection. Genes Dev 31:503-510

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