PATRICK M SUNG

..Recent progress on elucidating the mechanisms of action of Rad51 and Dmc1 and their cohorts of ancillary factors is reviewed here...

..Rad51 complex formation. The Rdh54 expression and purification procedures described here should facilitate the functional dissection of this DNA recombination/repair factor...

..These results provide evidence that DNA binding by the evolutionarily conserved amino terminus of Rad52 is needed for the capture of the second DNA end during homologous recombination...

..Continuing efforts with reconstituted systems that comprise yeast factors will undoubtedly continue to provide insights into the mechanistic intricacy of the homologous recombination machinery...

..These results, thus, establish Mph1 as an ATP-dependent DNA helicase, and the availability of purified Mph1 should facilitate efforts at deciphering the role of this protein in homologous recombination and mutation avoidance...

..The results thus clarify the role of BRCA2 in Rad51-dependent DNA recombination and repair, and the experimental strategies described herein should be valuable for systematically deciphering this BRCA2 function...

..Our data reveal a novel mechanism of substrate targeting in which sumoylation of a protein can help trigger its subsequent ubiquitination by recruiting a SUMO-binding ubiquitin ligase...

..Our results demonstrate the multifaceted role of PALB2 in chromosome damage repair. Because PALB2 mutations can cause cancer or Fanconi anemia, our findings shed light on the mechanism of tumor suppression in humans...

..These features of Rdh54 suggest a role of this protein factor in chromatin rearrangement during DNA recombination and repair...

..These findings shed light on the function of Hed1 and, importantly, unveil a novel mechanism for the regulation of homologous recombination...

..Our reconstituted system should serve as a useful model for delineating the mechanistic intricacy of the DNA break resection process in eukaryotes...

..Thus, our results unveil a bipartite mechanism of Hop2-Mnd1 in homologous DNA pairing: stabilization of the Rad51 presynaptic filament and duplex DNA capture to enhance synaptic complex formation...

..These results highlight the importance of the ATP hydrolysisfueled DNA motor activity in SRS2 functions...

..This function of the BLM-Topo IIIalpha-BLAP75 dissolvasome is likely indispensable for genome maintenance and cancer avoidance...

..Unlike the previously characterized members of the RecQ family, RECQ4 lacks a detectable DNA helicase activity...

..The manner in which Rad51 and Dmc1 functionally cooperate in meiotic recombination remains to be determined...

..Our results provide a mechanistic framework for rationalizing the multi-faceted role of Rad52 in recombination and DNA repair...

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..Moreover, our biochemical studies have helped identify A320V as a separation-of-function mutation in Rad51 with regards to a differential ablation of Rad52 interaction...

..Three recent studies, including work by Jackson and colleagues (pp. 2767- 2772) in the October 15, 2008, issue of Genes & Development, have begun to shed some light on the intricacy of this process...

..The DNA strand exchange activity of hDmc1 is probably indispensable for repair of DNA double-strand breaks during meiosis and for maintaining the ploidy of meiotic chromosomes...

..These results suggest that Rad54-mediated chromatin remodeling coincides with DNA homology search by the Rad51 presynaptic filament and that this process is facilitated by an interaction of Rad54 with histone H3...

..This reconstituted system provides researchers a biochemical means to dissect the mechanisms of the homologous recombination machinery...

..We also demonstrate that FANCI can be ubiquitinated on Lys-523 by the UBE2T-FANCL pair in vitro. These findings should facilitate future efforts directed at elucidating molecular aspects of the FA pathway...

..Importantly, Mph1, but not a helicase-defective variant, dissociates Rad51-made D-loops. Overall, the results from our analyses suggest a new role of Mph1 in promoting the noncrossover repair of DNA double-strand breaks...

..The biochemical systems established in this study should be useful for the continuing dissection of the action mechanism of Rdh54 and Dmc1...

..These results help form the basis for understanding the functions of ATP binding and ATP hydrolysis in hRad51-mediated recombination reactions...

..Sinha and colleagues also demonstrated that the DNA end-binding protein complex Ku regulates the activity of AdnAB...

..Defects in BLM are also associated with the cancer phenotype. The past several years have witnessed dramatic advances in our understanding of the mechanism and regulation of HR...

..These results highlight the importance of Rad51 interaction in the anti-recombinase function of Srs2, and provide evidence that this Srs2 function can be uncoupled from its helicase activity...

..This result provides proof that the functional integrity of the BTB complex is contingent upon the interaction of BLAP75 with Topo IIIalpha...

..These regulatory pathways function in parallel to promote the usage of the genome-preserving synthesis-dependent strand annealing HR pathway or otherwise suppress crossover formation...

..Our studies are therefore highly germane for cancer etiology, as the molecular information derived from them can be exploited to advance cancer diagnosis, prognosis and treatment. ..

..The results from our research endeavors have direct relevance to understanding the role of homologous recombination in cancer suppression. ..

..The results from our research endeavors will shed mechanistic light on BLM-dependent control mechanisms of HR and will provide an explanation for the genome instability and cancer susceptibility in BS patients. ..

..The results should shed some light on the mechanistic underpinnings of the homologous recombination machinery in human cells and will have important implications for cancer etiology and prevention. ..

..The studies should shed some light on the biological functions of the Rad51 paralogs and contribute to deciphering the mechanism of homologous recombinational repair in higher eukaryotic cells. ..

..The studies should provide insights about the mechanisms of the major recombination pathways in eukaryotic cells. ..

..Our studies are therefore highly germane for cancer etiology, as the molecular information derived from them can be exploited to advance cancer diagnosis, prognosis and treatment. ..

..For these reasons, the studies outlined in the renewal application have direct relevance to cancer biology and public health. ..

..The results from our research endeavors will shed mechanistic light on BLM-dependent control mechanisms of HR and will provide an explanation for the genome instability and cancer susceptibility in BS patients. ..

..For these reasons, the studies outlined in the renewal application have direct relevance to cancer biology and public health. ..

..abstract_text> ..

..These proposed studies represent the starting point in dissecting the molecular mechanism of homologous recombination and repair of chromosomal breakage in eukaryotes. ..

..The Msh4 and Msh5 proteins will be purified and biochemical studies will be carried out to test the hypothesis that they interact with the Holliday structure and with other recombination intermediates. ..

..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. ..