The Experts below are selected from a list of 44040 Experts worldwide ranked by ideXlab platform
Wei Xiao - One of the best experts on this subject based on the ideXlab platform.
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rev1 plays central roles in mammalian dna Damage Tolerance in response to uv irradiation
FEBS Journal, 2019Co-Authors: Wangyang Chen, Tonghui Bi, Mengxue Lu, Wei XiaoAbstract:: Rev1, a Y-family DNA polymerase, is involved in the Tolerance of DNA Damage by translesion DNA synthesis (TLS). Previous studies have shown that the C-terminal domain (CTD) and ubiquitin (Ub)-binding (UBM) domains of Rev1 play important roles in UV-Damage Tolerance, but how these domains contribute to the process remains unclear. In this study, we created Ub mutations in a proliferating cell nuclear antigen (PCNA)-Ub fusion that differentially affect its interaction with Rev1 and Polη and found that UV-Damage Tolerance depends on its interaction with Rev1 but not Polη. We also created Rev1-UBM mutations altering its interaction with a PCNA-Ub fusion and Rev1-CTD mutations affecting its interaction with Polη and the Rev7 subunit of Polζ. We thus demonstrated that elevated expression of Rev1 alone is sufficient to confer enhanced UV-Damage Tolerance and that this Tolerance depends on its physical interaction with monoubiquitinated PCNA and Polζ but is independent of Polη. Collectively, these studies reveal central roles played by Rev1 in coordinating UV-Damage response pathway choice in mammalian cells.
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error free dna Damage Tolerance in saccharomyces cerevisiae
Mutation Research-reviews in Mutation Research, 2015Co-Authors: Susan Blackwell, Wei Xiao, Zhoushuai Qin, Aiyang LinAbstract:DNA-Damage Tolerance (DDT) is an important mechanism for living cells to bypass replication blocks on the template strand. In Saccharomyces cerevisiae, DDT is mediated by the RAD6 epistasis group of genes, consisting of two parallel pathways: error-prone translesion DNA synthesis (TLS), and error-free lesion bypass. The two pathways are activated by sequential ubiquitination of PCNA on the Lys164 residue. When a replication fork is stalled at a lesion, PCNA is first monoubiquitinated by Rad6-Rad18, which leads to the TLS pathway. The subsequent ubiquitination by the Mms2-Ubc13-Rad5 complex on the monoubiquitinated PCNA is to form a Lys63-linked polyubiquitin chain that promotes error-free lesion bypass. While the TLS pathway has been extensively characterized, the molecular events leading to error-free lesion bypass by polyubiquitinated PCNA are largely obscure. Furthermore, PCNA can also be sumoylated at the same Lys164 residue, which helps to recruit Srs2, a helicase and anti-recombinase. This review summarizes recent advances in our understanding of error-free DDT and its interplay with Srs2 and homologous recombination.
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dna Damage Tolerance mediated by pcna ub fusions in human cells is dependent on rev1 but not polη
Nucleic Acids Research, 2013Co-Authors: Mengxue Lu, Xin Xu, Michelle Hanna, Naoko Shiomi, Wei XiaoAbstract:In response to replication-blocking lesions, proliferating cell nuclear antigen (PCNA) can be sequentially ubiquitinated at the K164 residue, leading to two modes of DNA-Damage Tolerance, namely, translesion DNA synthesis (TLS) and error-free lesion bypass. Although the majority of reported data support a model whereby monoubiquitinated PCNA enhances its affinity for TLS polymerases and hence recruits them to the Damage sites, this model has also been challenged by several observations. In this study, we expressed the PCNA-164R and ubiquitin (UB) fusion genes in an inducible manner in an attempt to mimic PCNA monoubiquitination in cultured human cells. It was found that expression of both N- and C-terminal PCNA•Ub fusions conferred significant Tolerance to ultraviolet (UV)-induced DNA Damage. Surprisingly, depletion of Polη, a TLS polymerase dedicated to bypassing UV-induced pyrimidine dimers, did not alter Tolerance conferred by PCNA•Ub. In contrast, depletion of Rev1, another TLS polymerase serving as a scaffold for the assembly of the TLS complex, completely abolished PCNA•Ub-mediated Damage Tolerance. Similar genetic interactions were confirmed when UV-induced monoubiquitination of endogenous PCNA is abolished by RAD18 deletion. Hence, PCNA•Ub fusions bypass the requirement for PCNA monoubiquitination, and UV Damage Tolerance conferred by these fusions is dependent on Rev1 but independent of Polη.
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roles of sequential ubiquitination of pcna in dna Damage Tolerance
FEBS Letters, 2011Co-Authors: Weiwei Zhang, Wei Xiao, Zhoushuai Qin, Xiaojie ZhangAbstract:Living organisms not only repair DNA Damage induced by environmental agents and endogenous cellular metabolites, but have also developed mechanisms to survive in the presence of otherwise lethal lesions. DNA-Damage Tolerance (DDT) is considered such a mechanism that resumes DNA synthesis in the presence of replication-blocking lesions. Recent studies revealed that DDT in budding yeast is achieved through sequential ubiquitination of DNA polymerase processivity factor, proliferating cell nuclear antigen (PCNA). It is generally believed that monoubiquitinated PCNA promotes translesion DNA synthesis, whereas polyubiquitinated PCNA mediates an error-free mode of lesion bypass. This review will discuss how ubiquitinated PCNA modulates different means of lesion bypass.
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arabidopsis thaliana ubc13 implication of error free dna Damage Tolerance and lys63 linked polyubiquitylation in plants
Plant Molecular Biology, 2006Co-Authors: Rui Wen, Lindsay Newton, Hong Wang, Wei XiaoAbstract:Ubiquitylation is an important biochemical reaction found in all eukaryotic organisms and is involved in a wide range of cellular processes. Conventional ubiquitylation requires the formation of polyubiquitin chains linked through Lys48 of the ubiquitin, which targets specific proteins for degradation. Recently polyubiquitylation through a noncanonical Lys63 chain has been reported, and is required for error-free DNA Damage Tolerance (or postreplication repair) in yeast. To date, Ubc13 is the only known ubiquitin-conjugating enzyme (Ubc) capable of catalyzing the Lys63-linked polyubiquitylation reaction and this function requires interaction with the Ubc variant Mms2. No information is available on either Lys63-linked ubiquitylation or error-free Damage Tolerance in plants. We thus cloned and functionally characterized two Arabidopsis thaliana UBC13 genes, AtUBC13A and AtUBC13B. The two genes are highly conserved with respect to chromosomal structure and protein sequence, suggesting that they are derived from a recent gene duplication event. Both AtUbc13 proteins are able to physically interact with yeast or human Mms2, implying that plants also employ the Lys63-linked polyubiquitylation reaction. Furthermore, AtUBC13 genes are able to functionally complement the yeast ubc13 null mutant for spontaneous mutagenesis and sensitivity to DNA damaging agents, suggesting the existence of an error-free DNA Damage Tolerance pathway in plants. The AtUBC13 genes appear to express ubiquitously and are not induced by various conditions tested.
Alena V Makarova - One of the best experts on this subject based on the ideXlab platform.
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dna Damage Tolerance by eukaryotic dna polymerase and primase primpol
International Journal of Molecular Sciences, 2017Co-Authors: Elizaveta O Boldinova, Paulina H Wanrooij, Evgeniy S Shilkin, Sjoerd Wanrooij, Alena V MakarovaAbstract:PrimPol is a human deoxyribonucleic acid (DNA) polymerase that also possesses primase activity and is involved in DNA Damage Tolerance, the prevention of genome instability and mitochondrial DNA ma ...
Stefan Jentsch - One of the best experts on this subject based on the ideXlab platform.
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DNA bending facilitates the error-free DNA Damage Tolerance pathway and upholds genome integrity
EMBO Journal, 2014Co-Authors: Víctor González-huici, Barnabas Szakal, Federica Castellucci, Demis Menolfi, Eerappa Rajakumara, Madhusoodanan Urulangodi, Ivan Psakhye, Rodrigo Bermejo, Marco Fumasoni, Stefan JentschAbstract:DNA replication is sensitive to Damage in the template. To bypass lesions and complete replication, cells activate recombination-mediated (error-free) and translesion synthesis-mediated (error-prone) DNA Damage Tolerance pathways. Crucial for error-free DNA Damage Tolerance is template switching, which depends on the formation and resolution of Damage-bypass intermediates consist-ing of sister chromatid junctions. Here we show that a chromatin architectural pathway involving the high mobility group box pro-tein Hmo1 channels replication-associated lesions into the error-free DNA Damage Tolerance pathway mediated by Rad5 and PCNA polyubiquitylation, while preventing mutagenic bypass and toxic recombination. In the process of template switching, Hmo1 also promotes sister chromatid junction formation predominantly dur-ing replication. Its C-terminal tail, implicated in chromatin bend-ing, facilitates the formation of catenations/hemicatenations and mediates the roles of Hmo1 in DNA Damage Tolerance pathway choice and sister chromatid junction formation. Together, the results suggest that replication-associated topological changes involving the molecular DNA bender, Hmo1, set the stage for dedi-cated repair reactions that limit errors during replication and impact on genome stability.
Karlene A Cimprich - One of the best experts on this subject based on the ideXlab platform.
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DNA Damage Tolerance: when it's OK to make mistakes
Nature Chemical Biology, 2009Co-Authors: Debbie J Chang, Karlene A CimprichAbstract:Mutations can be beneficial under conditions in which genetic diversity is advantageous, such as somatic hypermutation and antibody generation, but they can also be lethal when they disrupt basic cellular processes or cause uncontrolled proliferation and cancer. Mutations arise from inaccurate processing of lesions generated by endogenous and exogenous DNA damaging agents, and the genome is particularly vulnerable to such Damage during S phase. In this phase of the cell cycle, many lesions in the DNA template block replication. Such lesions must be bypassed in order to preserve fork stability and to ensure completion of DNA replication. Lesion bypass is carried out by a set of error-prone and error-free processes collectively referred to as DNA Damage Tolerance mechanisms. Here, we discuss how two types of DNA Damage Tolerance, translesion synthesis and template switching, are regulated at stalled replication forks by ubiquitination of PCNA, and the conditions under which they occur.
Qunxin She - One of the best experts on this subject based on the ideXlab platform.
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a unique b family dna polymerase facilitating error prone dna Damage Tolerance in crenarchaeota
Frontiers in Microbiology, 2020Co-Authors: Xu Feng, Xiaotong Liu, Ruiliang Zhao, Wenqian Feng, Jianglan Liao, Wenyuan Han, Qunxin SheAbstract:Sulfolobus islandicus codes for four DNA polymerases: three are of the B-family (Dpo1, Dpo2, and Dpo3), and one is of the Y-family (Dpo4). Western analysis revealed that among the four polymerases, only Dpo2 exhibited DNA Damage-inducible expression. To investigate how these DNA polymerases could contribute to DNA Damage Tolerance in S. islandicus, we conducted genetic analysis of their encoding genes in this archaeon. Plasmid-borne gene expression revealed that Dpo2 increases cell survival upon DNA Damage at the expense of mutagenesis. Gene deletion studies showed although dpo1 is essential, the remaining three genes are dispensable. Furthermore, although Dpo4 functions in housekeeping translesion DNA synthesis (TLS), Dpo2, a B-family DNA polymerase once predicted to be inactive, functions as a Damage-inducible TLS enzyme solely responsible for targeted mutagenesis, facilitating GC to AT/TA conversions in the process. Together, our data indicate that Dpo2 is the main DNA polymerase responsible for DNA Damage Tolerance and is the primary source of targeted mutagenesis. Given that crenarchaea encoding a Dpo2 also have a low-GC composition genome, the Dpo2-dependent DNA repair pathway may be conserved in this archaeal lineage.
