scholarly journals The role of the Fanconi anemia pathway in DNA repair and maintenance of genome stability

2014 ◽  
Vol 68 ◽  
pp. 459-472 ◽  
Author(s):  
Aleksandra M. Koczorowska ◽  
Aneta Białkowska ◽  
Katarzyna Kluzek ◽  
Małgorzata Z. Zdzienicka
Keyword(s):  
Dna Repair ◽  
Fanconi Anemia ◽  
Genome Stability ◽  
Fanconi Anemia Pathway

scholarly journals Regulation of the Fanconi Anemia DNA Repair Pathway by Phosphorylation and Monoubiquitination

Genes ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1763
Author(s):  
Masamichi Ishiai
Keyword(s):  
Dna Repair ◽  
Fanconi Anemia ◽  
Genome Stability ◽  
Short Review ◽  
Repair Pathway ◽  
Binding Partner ◽  
Interstrand Crosslinks ◽  
Pathway Activation ◽  
Dna Interstrand Crosslinks

The Fanconi anemia (FA) DNA repair pathway coordinates a faithful repair mechanism for stalled DNA replication forks caused by factors such as DNA interstrand crosslinks (ICLs) or replication stress. An important role of FA pathway activation is initiated by monoubiquitination of FANCD2 and its binding partner of FANCI, which is regulated by the ATM-related kinase, ATR. Therefore, regulation of the FA pathway is a good example of the contribution of ATR to genome stability. In this short review, we summarize the knowledge accumulated over the years regarding how the FA pathway is activated via phosphorylation and monoubiquitination.

scholarly journals The Fanconi Anemia Pathway Maintains Genome Stability by Coordinating Replication and Transcription

2015 ◽  
Vol 60 (3) ◽  
pp. 351-361 ◽  
Author(s):  
Rebekka A. Schwab ◽  
Jadwiga Nieminuszczy ◽  
Fenil Shah ◽  
Jamie Langton ◽  
David Lopez Martinez ◽  
...  
Keyword(s):  
Fanconi Anemia ◽  
Genome Stability ◽  
Fanconi Anemia Pathway

scholarly journals The Role of Posttranslational Modifications in DNA Repair

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Miaomiao Bai ◽  
Dongdong Ti ◽  
Qian Mei ◽  
Jiejie Liu ◽  
Xin Yan ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Genome Stability ◽  
Protein Localization ◽  
Complex Structure ◽  
Protein Protein Interactions ◽  
Regulate Protein

The human body is a complex structure of cells, which are exposed to many types of stress. Cells must utilize various mechanisms to protect their DNA from damage caused by metabolic and external sources to maintain genomic integrity and homeostasis and to prevent the development of cancer. DNA damage inevitably occurs regardless of physiological or abnormal conditions. In response to DNA damage, signaling pathways are activated to repair the damaged DNA or to induce cell apoptosis. During the process, posttranslational modifications (PTMs) can be used to modulate enzymatic activities and regulate protein stability, protein localization, and protein-protein interactions. Thus, PTMs in DNA repair should be studied. In this review, we will focus on the current understanding of the phosphorylation, poly(ADP-ribosyl)ation, ubiquitination, SUMOylation, acetylation, and methylation of six typical PTMs and summarize PTMs of the key proteins in DNA repair, providing important insight into the role of PTMs in the maintenance of genome stability and contributing to reveal new and selective therapeutic approaches to target cancers.

scholarly journals Inhibition of USP28 overcomes Cisplatin-Resistance of Squamous Tumors by Suppression of the Fanconi Anemia Pathway

2020 ◽  
Author(s):  
Cristian Prieto-Garcia ◽  
Oliver Hartmann ◽  
Michaela Reissland ◽  
Thomas Fischer ◽  
Carina R. Maier ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Tumor Cells ◽  
Dna Damage Response ◽  
Fanconi Anemia ◽  
Cisplatin Resistance ◽  
Chemotherapy Resistance ◽  
Fanconi Anemia Pathway ◽  
Platinum Based Chemotherapy ◽  
Damage Response

AbstractSquamous cell carcinomas (SCC) frequently have a limited response to or develop resistance to platinum-based chemotherapy, and have an exceptionally high tumor mutational burden. As a consequence, overall survival is limited and novel therapeutic strategies are urgently required, especially in light of a rising incidences. SCC tumors express ΔNp63, a potent regulator of the Fanconi Anemia (FA) DNA-damage response pathway during chemotherapy, thereby directly contributing to chemotherapy-resistance. Here we report that the deubiquitylase USP28 affects the FA DNA repair pathway during cisplatin treatment in SCC, thereby influencing therapy outcome. In an ATR-dependent fashion, USP28 is phosphorylated and activated to positively regulate the DNA damage response. Inhibition of USP28 reduces recombinational repair via an ΔNp63-Fanconi Anemia pathway axis, and weakens the ability of tumor cells to accurately repair DNA. Our study presents a novel mechanism by which tumor cells, and in particular ΔNp63 expressing SCC, can be targeted to overcome chemotherapy resistance.SignificanceLimited treatment options and low response rates to chemotherapy are particularly common in patients with squamous cancer. The SCC specific transcription factor ΔNp63 enhances the expression of Fanconi Anemia genes, thereby contributing to recombinational DNA repair and Cisplatin resistance. Targeting the USP28-ΔNp63 axis in SCC tones down this DNA damage response pathways, thereby sensitizing SCC cells to cisplatin treatment.

scholarly journals The role of the Fanconi anemia pathway in the pathophysiology of ovarian cancer

2015 ◽  
Vol 86 (2) ◽  
pp. 150-154
Author(s):  
Agnieszka Synowiec ◽  
Jolanta Szenajch ◽  
Gabriel Wcisło ◽  
Cezary Szczylik
Keyword(s):  
Ovarian Cancer ◽  
Fanconi Anemia ◽  
Fanconi Anemia Pathway

scholarly journals The Fanconi Anemia Pathway of DNA Repair and Human Cancer

10.5772/59995 ◽  
2015 ◽  
Author(s):  
Vaidehi Krishnan ◽  
Lavina Sierra Tay ◽  
Yoshiaki Ito
Keyword(s):  
Dna Repair ◽  
Fanconi Anemia ◽  
Human Cancer ◽  
Fanconi Anemia Pathway

scholarly journals Fanconi anemia pathway and its relationship with cancer

2021 ◽  
Author(s):  
Chenchen Dan ◽  
Hongjing Pei ◽  
Buzhe Zhang ◽  
Xuan Zheng ◽  
Dongmei Ran ◽  
...  
Keyword(s):  
Fanconi Anemia ◽  
Genome Stability ◽  
Excision Repair ◽  
Cancer Therapies ◽  
Repair Pathway ◽  
Hematological Disease ◽  
Interstrand Crosslink ◽  
Nucleotide Excision ◽  
Associated Proteins

AbstractFanconi Anemia (FA) is a rare inherited hematological disease, caused by mutations in genes involved in the DNA interstrand crosslink (ICL) repair. Up to date, 22 genes have been identified that encode a series of functionally associated proteins that recognize ICL lesion and mediate the activation of the downstream DNA repair pathway including nucleotide excision repair, translesion synthesis, and homologous recombination. The FA pathway is strictly regulated by complex mechanisms such as ubiquitination, phosphorylation, and degradation signals that are essential for the maintenance of genome stability. Here, we summarize the discovery history and recent advances of the FA genes, and further discuss the role of FA pathway in carcinogenesis and cancer therapies.

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