Pub Date : 2021-06-01DOI: 10.1007/s42764-021-00042-1
Yidan Liu, Lin-Yu Lu
{"title":"BRCA1: a key player at multiple stages of homologous recombination in DNA double-strand break repair","authors":"Yidan Liu, Lin-Yu Lu","doi":"10.1007/s42764-021-00042-1","DOIUrl":"https://doi.org/10.1007/s42764-021-00042-1","url":null,"abstract":"","PeriodicalId":73144,"journal":{"name":"Genome instability & disease","volume":"2 1","pages":"164-174"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s42764-021-00042-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52772154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-01DOI: 10.1007/s42764-021-00038-x
Fadi Abboodi, Nella C. Delva, Jennifer Emmel, Ariana N. Renrick, P. Buckhaults, Carolyn E. Banister, K. Creek, L. Pirisi
{"title":"Human papillomavirus-mediated carcinogenesis and tumor progression","authors":"Fadi Abboodi, Nella C. Delva, Jennifer Emmel, Ariana N. Renrick, P. Buckhaults, Carolyn E. Banister, K. Creek, L. Pirisi","doi":"10.1007/s42764-021-00038-x","DOIUrl":"https://doi.org/10.1007/s42764-021-00038-x","url":null,"abstract":"","PeriodicalId":73144,"journal":{"name":"Genome instability & disease","volume":"2 1","pages":"71-91"},"PeriodicalIF":0.0,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s42764-021-00038-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52771882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-01DOI: 10.1007/s42764-021-00032-3
Taewan Kim
{"title":"LncRNAs as key players in the MYC pathways","authors":"Taewan Kim","doi":"10.1007/s42764-021-00032-3","DOIUrl":"https://doi.org/10.1007/s42764-021-00032-3","url":null,"abstract":"","PeriodicalId":73144,"journal":{"name":"Genome instability & disease","volume":"2 1","pages":"24-38"},"PeriodicalIF":0.0,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s42764-021-00032-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52771794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-01DOI: 10.1007/s42764-020-00027-6
Wouter Huiting, Steven Bergink
{"title":"Locked in a vicious cycle: the connection between genomic instability and a loss of protein homeostasis","authors":"Wouter Huiting, Steven Bergink","doi":"10.1007/s42764-020-00027-6","DOIUrl":"https://doi.org/10.1007/s42764-020-00027-6","url":null,"abstract":"","PeriodicalId":73144,"journal":{"name":"Genome instability & disease","volume":"2 1","pages":"1-23"},"PeriodicalIF":0.0,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s42764-020-00027-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52771690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-01Epub Date: 2021-01-02DOI: 10.1007/s42764-020-00030-x
Sang-In Kim, Gerd P Pfeifer
In mammals, DNA methyltransferases create 5-methylcytosines (5mC) predominantly at CpG dinucleotides. 5mC oxidases convert 5mC in three consecutive oxidation steps to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and then 5-carboxylcytosine (5caC). Upon irradiation with UV light, dipyrimidines containing C, 5mC and 5hmC are known to form cyclobutane pyrimidine dimers (CPDs) as major DNA photolesions. However, the photobiology of 5fC and 5caC has remained largely unexplored. Here, we tested a series of oligonucleotides with single or multiple positions carrying cytosine (C), 5mC, 5hmC, 5fC or 5caC and irradiated them with different sources of UV irradiation. While UVC radiation produced CPDs near dipyrimidines containing all types of modified cytosine bases, UVB radiation produced by far the highest levels of CPDs near 5caC-containing sequences. Dipyrimidines one or two nucleotide positions adjacent to 5caC but not always those involving this modified base directly were the major sites for these prominent UVB photoproducts. This selectivity did not depend on whether 5caC was present on one or both DNA strands at CpG sequences. We also observed a tendency of the 5caC-containing DNA strands to undergo apparent covalent crosslinking. This reaction occurred with UVB or UVC but not with UVA irradiation. Our data show that 5-carboxylcytosine, although generally a rare base in the genome, can nonetheless make a strong contribution to sequence-specific DNA damage perhaps by acting as a DNA-intrinsic photosensitizer.
{"title":"The epigenetic DNA modification 5-carboxylcytosine promotes high levels of cyclobutane pyrimidine dimer formation upon UVB irradiation.","authors":"Sang-In Kim, Gerd P Pfeifer","doi":"10.1007/s42764-020-00030-x","DOIUrl":"10.1007/s42764-020-00030-x","url":null,"abstract":"<p><p>In mammals, DNA methyltransferases create 5-methylcytosines (5mC) predominantly at CpG dinucleotides. 5mC oxidases convert 5mC in three consecutive oxidation steps to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and then 5-carboxylcytosine (5caC). Upon irradiation with UV light, dipyrimidines containing C, 5mC and 5hmC are known to form cyclobutane pyrimidine dimers (CPDs) as major DNA photolesions. However, the photobiology of 5fC and 5caC has remained largely unexplored. Here, we tested a series of oligonucleotides with single or multiple positions carrying cytosine (C), 5mC, 5hmC, 5fC or 5caC and irradiated them with different sources of UV irradiation. While UVC radiation produced CPDs near dipyrimidines containing all types of modified cytosine bases, UVB radiation produced by far the highest levels of CPDs near 5caC-containing sequences. Dipyrimidines one or two nucleotide positions adjacent to 5caC but not always those involving this modified base directly were the major sites for these prominent UVB photoproducts. This selectivity did not depend on whether 5caC was present on one or both DNA strands at CpG sequences. We also observed a tendency of the 5caC-containing DNA strands to undergo apparent covalent crosslinking. This reaction occurred with UVB or UVC but not with UVA irradiation. Our data show that 5-carboxylcytosine, although generally a rare base in the genome, can nonetheless make a strong contribution to sequence-specific DNA damage perhaps by acting as a DNA-intrinsic photosensitizer.</p>","PeriodicalId":73144,"journal":{"name":"Genome instability & disease","volume":"2 1","pages":"59-69"},"PeriodicalIF":0.0,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415257/pdf/nihms-1659482.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39389528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-01DOI: 10.1007/s42764-021-00047-w
Siyu Chen, James P Lees-Miller, Yuan He, Susan P Lees-Miller
DNA-dependent protein kinase catalytic subunit DNA-PKcs/PRKDC is the largest serine/threonine protein kinase of the phosphatidyl inositol 3-kinase-like protein kinase (PIKK) family and is the most highly expressed PIKK in human cells. With its DNA-binding partner Ku70/80, DNA-PKcs is required for regulated and efficient repair of ionizing radiation-induced DNA double-strand breaks via the non-homologous end joining (NHEJ) pathway. Loss of DNA-PKcs or other NHEJ factors leads to radiation sensitivity and unrepaired DNA double-strand breaks (DSBs), as well as defects in V(D)J recombination and immune defects. In this review, we highlight the contributions of the late Dr. Carl W. Anderson to the discovery and early characterization of DNA-PK. We furthermore build upon his foundational work to provide recent insights into the structure of NHEJ synaptic complexes, an evolutionarily conserved and functionally important YRPD motif, and the role of DNA-PKcs and its phosphorylation in NHEJ. The combined results identify DNA-PKcs as a master regulator that is activated by its detection of two double-strand DNA ends for a cascade of phosphorylation events that provide specificity and efficiency in assembling the synaptic complex for NHEJ.
dna依赖性蛋白激酶催化亚基DNA-PKcs/PRKDC是磷脂酰肌醇3激酶样蛋白激酶(PIKK)家族中最大的丝氨酸/苏氨酸蛋白激酶,是人类细胞中表达量最高的PIKK。DNA- pkcs与其DNA结合伙伴Ku70/80一起,通过非同源末端连接(non-homologous end joining, NHEJ)途径调控和有效修复电离辐射诱导的DNA双链断裂。DNA- pkcs或其他NHEJ因子的缺失导致辐射敏感性和未修复的DNA双链断裂(DSBs),以及V(D)J重组缺陷和免疫缺陷。在这篇综述中,我们强调了已故的卡尔·w·安德森博士对DNA-PK的发现和早期表征的贡献。我们进一步以他的基础工作为基础,提供了对NHEJ突触复合物结构的最新见解,这是一个进化上保守且功能重要的YRPD基序,以及DNA-PKcs及其磷酸化在NHEJ中的作用。综合结果确定DNA- pkcs是一个主调节因子,通过检测两条双链DNA末端来激活一系列磷酸化事件,这些磷酸化事件为NHEJ的突触复合体的组装提供了特异性和效率。
{"title":"Structural insights into the role of DNA-PK as a master regulator in NHEJ.","authors":"Siyu Chen, James P Lees-Miller, Yuan He, Susan P Lees-Miller","doi":"10.1007/s42764-021-00047-w","DOIUrl":"https://doi.org/10.1007/s42764-021-00047-w","url":null,"abstract":"<p><p>DNA-dependent protein kinase catalytic subunit DNA-PKcs/<i>PRKDC</i> is the largest serine/threonine protein kinase of the phosphatidyl inositol 3-kinase-like protein kinase (PIKK) family and is the most highly expressed PIKK in human cells. With its DNA-binding partner Ku70/80, DNA-PKcs is required for regulated and efficient repair of ionizing radiation-induced DNA double-strand breaks via the non-homologous end joining (NHEJ) pathway. Loss of DNA-PKcs or other NHEJ factors leads to radiation sensitivity and unrepaired DNA double-strand breaks (DSBs), as well as defects in V(D)J recombination and immune defects. In this review, we highlight the contributions of the late Dr. Carl W. Anderson to the discovery and early characterization of DNA-PK. We furthermore build upon his foundational work to provide recent insights into the structure of NHEJ synaptic complexes, an evolutionarily conserved and functionally important YRPD motif, and the role of DNA-PKcs and its phosphorylation in NHEJ. The combined results identify DNA-PKcs as a master regulator that is activated by its detection of two double-strand DNA ends for a cascade of phosphorylation events that provide specificity and efficiency in assembling the synaptic complex for NHEJ.</p>","PeriodicalId":73144,"journal":{"name":"Genome instability & disease","volume":"2 4","pages":"195-210"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s42764-021-00047-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9587807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-01Epub Date: 2021-03-26DOI: 10.1007/s42764-021-00035-0
Yafang Shang, Fei-Long Meng
The adaptive immune system can diversify the antigen receptors to eliminate various pathogens through programmed DNA lesions at antigen receptor genes. In immune diversification, general DNA repair machineries are applied to transform the programmed DNA lesions into gene mutation or recombination events with common and unique features. Here we focus on antibody class switch recombination (CSR), and review the initiation of base damages, the conversion of damaged base to DNA double-strand break, and the ligation of broken ends. With an emphasis on the unique features in CSR, we discuss recent advances in the understanding of DNA repair/replication coordination, and ERCC6L2-mediated deletional recombination. We further elaborate the application of CSR in end-joining, resection and translesion synthesis assays. In the time of the COVID-19 pandemic, we hope it help to understand the generation of therapeutic antibodies.
{"title":"Repair of programmed DNA lesions in antibody class switch recombination: common and unique features.","authors":"Yafang Shang, Fei-Long Meng","doi":"10.1007/s42764-021-00035-0","DOIUrl":"https://doi.org/10.1007/s42764-021-00035-0","url":null,"abstract":"<p><p>The adaptive immune system can diversify the antigen receptors to eliminate various pathogens through programmed DNA lesions at antigen receptor genes. In immune diversification, general DNA repair machineries are applied to transform the programmed DNA lesions into gene mutation or recombination events with common and unique features. Here we focus on antibody class switch recombination (CSR), and review the initiation of base damages, the conversion of damaged base to DNA double-strand break, and the ligation of broken ends. With an emphasis on the unique features in CSR, we discuss recent advances in the understanding of DNA repair/replication coordination, and ERCC6L2-mediated deletional recombination. We further elaborate the application of CSR in end-joining, resection and translesion synthesis assays. In the time of the COVID-19 pandemic, we hope it help to understand the generation of therapeutic antibodies.</p>","PeriodicalId":73144,"journal":{"name":"Genome instability & disease","volume":"2 2","pages":"115-125"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s42764-021-00035-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25561505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-11-01DOI: 10.1007/s42764-020-00024-9
R. Kumar
{"title":"A new insight into base excision repair (BER) in targeted cancer therapy","authors":"R. Kumar","doi":"10.1007/s42764-020-00024-9","DOIUrl":"https://doi.org/10.1007/s42764-020-00024-9","url":null,"abstract":"","PeriodicalId":73144,"journal":{"name":"Genome instability & disease","volume":"1 1","pages":"310-317"},"PeriodicalIF":0.0,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s42764-020-00024-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52771298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}