a network of multi-tasking proteins at the dna replication fork preserves genome stability一个多任务网络蛋白质的dna复制叉保持基因组稳定性.pdfVIP
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a network of multi-tasking proteins at the dna replication fork preserves genome stability一个多任务网络蛋白质的dna复制叉保持基因组稳定性
A Network of Multi-Tasking Proteins
at the DNA Replication Fork
Preserves Genome Stability
1 2,3 1 1 2,3 1*
Martin E. Budd , Amy Hin Yan Tong , Piotr Polaczek , Xiao Peng , Charles Boone , Judith L. Campbell
1 Braun Laboratories, California Institute of Technology, Pasadena, California, United States of America, 2 Banting and Best Department of Medical Research, University of
Toronto, Toronto, Ontario, Canada, 3 Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Ontario, Canada
To elucidate the network that maintains high fidelity genome replication, we have introduced two conditional mutant
alleles of DNA2, an essential DNA replication gene, into each of the approximately 4,700 viable yeast deletion mutants
and determined the fitness of the double mutants. Fifty-six DNA2-interacting genes were identified. Clustering analysis
of genomic synthetic lethality profiles of each of 43 of the DNA2-interacting genes defines a network (consisting of 322
genes and 876 interactions) whose topology provides clues as to how replication proteins coordinate regulation and
repair to protect genome integrity. The results also shed new light on the functions of the query gene DNA2, which,
despite many years of study, remain controversial, especially its proposed role in Okazaki fragment processing and the
nature of its in vivo substrates. Because of the multifunctional nature of virtually all proteins at the replication fork, the
meaning of any single genetic interaction is inherently ambiguous. The multiplexing nature of the current studies,
however, combined with follow-up supporting experiments, reveals most if not all of the unique pathways requiring
Dna2p. These include not only Okazaki fragment processing and DNA repair but also chromatin dynamics.
Citation: Budd M
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