Sang Eun Lee

..Permanent preanaphase arrest of srs2Delta cells is reversed by the addition of caffeine after cells have arrested. Thus, in addition to its roles in recombination, Srs2p appears to be needed to turn off the DNA damage checkpoint...

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..Sae2 and Tel1 promote MMEJ but inhibit NHEJ, likely by regulating Mre11-dependent ssDNA accumulation at DNA break. Our data support the role of Sae2 and Tel1 in MMEJ and genome integrity...

..These pathways select proper homologous templates or broken DNA ends for the faithful repair of DNA breaks to avoid undesirable chromosomal translocations...

..This study provides molecular insights into how chromatin remodeling contributes to DNA repair and maintenance of chromatin fidelity in the face of DNA damage...

..However, Mre11 nuclease activity is essential for resection in the absence of extensive resection enzymes. The results provide new insights into how MRX catalyses end resection and recombination initiation...

..Deletion of SAW1 abolished association of Rad1 at SSA intermediates in vivo. We propose that Saw1 targets Rad1/Rad10 to Rad52-coated recombination intermediates...

..The interaction of Rsc1p with Mre11p appears to be vital for survival from genotoxic stress. These results suggest that chromatin remodeling by RSC is important for NHEJ...

..We propose that RSC-mediated chromatin remodeling at the DSB prepares chromatin to allow repair machinery to access the break and is vital for efficient DSB repair...

..The increased gamma ray sensitivity of rad1Delta rad52Delta yku70Delta strains compared to rad52Delta yku70Delta strains suggests that MMEJ also contributes to the repair of DSBs induced by ionizing radiation...

..Therefore, Dnl4-Lif1 plays an important part in determining repair pathway choice by participating at an early stage of DSB engagement in addition to providing the DNA ligase activity that completes NHEJ...

..Expression of excess Ku can partially offset the inhibition of end joining at G(2). The results suggest that regulation of Ku/Dnl4-Lif1 affinity for DNA ends may contribute to the cell cycle-dependent modulation of NHEJ efficiency...

..MHMR catalyzes chromosomal translocation almost as efficiently as intra-chromosomal repair. The results suggest that the intrinsic annealing propensity between microhomology sequences efficiently leads to chromosomal rearrangements...

..These results provide important insights into the early steps of DSB repair in eukaryotes...

..We further report that this Mec1-independent pathway converges with the Rad53/Dun1-regulated checkpoint kinase cascade and leads to the degradation of the ribonucleotide reductase inhibitor Sml1...

..We suggest that monitoring of the extent of DNA damage depends on independent binding of RPA and Rad52p to ssDNA, with Rad52p's activity modulated by Rad51p whereas RPA's action depends on Tid1p...

..In vivo and in vitro evidence suggests that phosphorylated forms of Ptc2 and Ptc3 specifically bind to the Rad53 FHA1 domain and inactivate Rad53-dependent pathways during adaptation and recovery by dephosphorylating Rad53...

..We propose that at least two separate activities associated with the N-terminus of Mre11p are required for its mitotic function...

..Furthermore, spontaneous RPA foci at DSBs are destabilized by the mph1Delta mutation. Therefore, Mph1p promotes GCR formation by partially suppressing HR, likely through its interaction with RPA...

..The information gleaned from the proposal will also provide a logical framework as to how cells tolerate cancer therapeutic agent-induced DNA lesions and shed lights on the prevention and improved therapeutic intervention of cancers. ..

..This application will identify and characterize damage- surveillance and other mechanisms that suppress chromosome translocation to understand the defects in blood cancers and develop novel preventive and/or therapeutic strategies. ..

..The information gleaned from the proposal will also provide a logical framework as to how cells tolerate cancer therapeutic agent-induced DNA lesions and shed lights on the prevention and improved therapeutic intervention of cancers. ..

..Since the components of DSB repair are conserved from yeast to humans, the insights garnered from our research will be valuable for dissecting the equivalent process in human cells and will be of relevance to public health. ..

..Furthermore, since DSB repair by NHEJ is remarkably conserved from yeast to humans, these studies will help to dissect the similar pathways in humans. ..

..This application will identify and characterize damage- surveillance and other mechanisms that suppress chromosome translocation to understand the defects in blood cancers and develop novel preventive and/or therapeutic strategies. ..