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Yi C.,Peking University | Yi C.,Peking Tsinghua Center for Life science | He C.,University of Chicago
Cold Spring Harbor Perspectives in Biology | Year: 2013

Endogenous and exogenous factors constantly challenge cellular DNA, generating cytotoxic and/or mutagenic DNA adducts. As a result, organisms have evolved different mechanisms to defend against the deleterious effects of DNA damage. Among these diverse repair pathways, direct DNA-repair systems provide cells with simple yet efficient solutions to reverse covalentDNA adducts. In this review,we focus on recent advances in the field of directDNA repair, namely, photolyase-, alkyltransferase-, and dioxygenase-mediated repair processes. We present specific examples to describe new findings of known enzymes and appealing discoveries of new proteins. At the end of this article, we also briefly discuss the influence of direct DNA repair on other fields of biology and its implication on the discovery of new biology. © 2013 Cold Spring Harbor Laboratory Press; all rights reserved. Source


Chang Y.-J.,Peking University | Huang X.-J.,Peking Tsinghua Center for Life science
Bone Marrow Transplantation | Year: 2014

Research on the different mechanisms for crossing HLA barriers has progressed over the past 10 years. General outlines have come into view for a solution to this issue and are often presented as 'haploidentical SCT' immunology. In this review, we discuss several mechanisms that have recently been described in ex vivo and in vivo settings that can either avoid GVHD or promote hematopoietic reconstitution in haploidentical settings. The host and donor T-cell responses to allogeneic HLA molecules are a fundamental obstacle to the successful application of haploidentical transplantation, which results in unacceptably high incidences of GVHD and graft rejection. Thus, the T-cell response is a central factor in the establishment of a novel haploidentical transplant protocol with superior outcomes. © 2014 Macmillan Publishers Limited. Source


Song C.-X.,University of Chicago | Yi C.,Peking University | Yi C.,Peking Tsinghua Center for Life science | He C.,University of Chicago
Nature Biotechnology | Year: 2012

Nucleotide variants, especially those related to epigenetic functions, provide critical regulatory information beyond simple genomic sequence, and they define cell status in higher organisms. 5-methylcytosine, which is found in DNA, was until recently the only nucleotide variant studied in terms of epigenetics in eukaryotes. However, 5-methylcytosine has turned out to be just one component of a dynamic DNA epigenetic regulatory network that also includes 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. Recently, reversible methylation of N 6 -methyladenosine in RNA has also been demonstrated. The discovery of these new nucleotide variants triggered an explosion of new information in the epigenetics field. This rapid research progress has benefited significantly from timely developments of new technologies that specifically recognize, enrich and sequence nucleotide modifications, as evidenced by the wide application of the bisulfite sequencing of 5-methylcytosine and very recent modifications of bisulfite sequencing to resolve 5-hydroxymethylcytosine from 5-methylcytosine with base-resolution information. © 2012 Nature America, Inc. Source


Yang M.,CAS Beijing National Laboratory for Molecular | Li J.,CAS Beijing National Laboratory for Molecular | Chen P.R.,CAS Beijing National Laboratory for Molecular | Chen P.R.,Peking Tsinghua Center for Life science
Chemical Society Reviews | Year: 2014

Considerable attention has been focused on improving the biocompatibility of Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC), a hallmark of bioorthogonal reaction, in living cells. Besides creating copper-free versions of click chemistry such as strain promoted azide-alkyne cycloaddition (SPAAC), a central effort has also been made to develop various Cu(i) ligands that can prevent the cytotoxicity of Cu(i) ions while accelerating the CuAAC reaction. Meanwhile, additional transition metals such as palladium have been explored as alternative sources to promote a bioorthogonal conjugation reaction on cell surface, as well as within an intracellular environment. Furthermore, transition metal mediated chemical conversions beyond conjugation have also been utilized to manipulate protein activity within living systems. We highlight these emerging examples that significantly enriched our protein chemistry toolkit, which will likely expand our view on the definition and applications of bioorthogonal chemistry. © 2014 the Partner Organisations. Source


Chang Y.-J.,Peking University | Zhao X.-Y.,Peking University | Huang X.-J.,Peking University | Huang X.-J.,Peking Tsinghua Center for Life science
Biology of Blood and Marrow Transplantation | Year: 2014

Haploidentical hematopoietic stem cell transplantation (HSCT) offers the benefits of rapid and nearly universal donor availability and has been accepted worldwide as an alternative treatment for patients with hematologic malignancies who do not have a completely HLA-matched sibling or who require urgent transplantation. Unfortunately, serious infections and leukemia relapse resulting from slow immune reconstitution remain the 2 most frequent causes of mortality in patients undergoing haploidentical HSCT, particularly in those receiving extensively T cell-depleted megadose CD34+ allografts. This review summarizes advances in immune recovery after haploidentical HSCT, focusing on the immune subsets likely to have the greatest impact on clinical outcomes. The progress made in accelerating immune reconstitution using different strategies after haploidentical HSCT is also discussed. It is our belief that a predictive immune subset-guided strategy to improve immune recovery might represent a future clinical direction. © 2014 American Society for Blood and Marrow Transplantation. Source

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