scholarly journals Role of Tip60 tumor suppressor in DNA repair pathway

2011 ◽  
Vol 56 (12) ◽  
pp. 1212-1215 ◽  
Author(s):  
ZhiJian Liu ◽  
YingLi Sun
Keyword(s):  
Dna Repair ◽  
Tumor Suppressor ◽  
Repair Pathway

scholarly journals Regulation of the cognitive aging process by the transcriptional repressor RP58

2021 ◽  
Author(s):  
Tomoko Tanaka ◽  
Shinobu Hirai ◽  
Hiroyuki Manabe ◽  
Kentaro Endo ◽  
Hiroko Shimbo ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Knockout Mice ◽  
Cognitive Aging ◽  
Critical Role ◽  
Harmful Effect ◽  
Transcriptional Repressor ◽  
Repair Pathway ◽  
Wild Type

Aging involves a decline in physiology which is a natural event in all living organisms. An accumulation of DNA damage contributes to the progression of aging. DNA is continually damaged by exogenous sources and endogenous sources. If the DNA repair pathway operates normally, DNA damage is not life threatening. However, impairments of the DNA repair pathway may result in an accumulation of DNA damage, which has a harmful effect on health and causes an onset of pathology. RP58, a zinc-finger transcriptional repressor, plays a critical role in cerebral cortex formation. Recently, it has been reported that the expression level of RP58 decreases in the aged human cortex. Furthermore, the role of RP58 in DNA damage is inferred by the involvement of DNMT3, which acts as a co-repressor for RP58, in DNA damage. Therefore, RP58 may play a crucial role in the DNA damage associated with aging. In the present study, we investigated the role of RP58 in aging. We used RP58 hetero-knockout and wild-type mice in adolescence, adulthood, or old age. We performed immunohistochemistry to determine whether microglia and DNA damage markers responded to the decline in RP58 levels. Furthermore, we performed an object location test to measure cognitive function, which decline with age. We found that the wild-type mice showed an increase in single-stranded DNA and gamma-H2AX foci. These results indicate an increase in DNA damage or dysfunction of DNA repair mechanisms in the hippocampus as age-related changes. Furthermore, we found that, with advancing age, both the wild-type and hetero-knockout mice showed an impairment of spatial memory for the object and increase in reactive microglia in the hippocampus. However, the RP58 hetero-knockout mice showed these symptoms earlier than the wild-type mice did. These results suggest that a decline in RP58 level may lead to the progression of aging.

scholarly journals Role of Fanconi DNA repair pathway in neural stem cell homeostasis

Cell Cycle ◽  
2008 ◽  
Vol 7 (13) ◽  
pp. 1911-1915 ◽  
Author(s):  
Karine Sii-Felice ◽  
Vilma Barroca ◽  
Olivier Etienne ◽  
Lydia Riou ◽  
Françoise Hoffschir ◽  
...  
Keyword(s):  
Dna Repair ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Repair Pathway ◽  
Cell Homeostasis

scholarly journals Role of Mammalian Rad54 in Telomere Length Maintenance

2003 ◽  
Vol 23 (16) ◽  
pp. 5572-5580 ◽  
Author(s):  
Isabel Jaco ◽  
Purificación Muñoz ◽  
Fermín Goytisolo ◽  
Joanna Wesoly ◽  
Susan Bailey ◽  
...  
Keyword(s):  
Dna Repair ◽  
Telomere Length ◽  
Essential Role ◽  
Repair Pathway ◽  
Wild Type ◽  
Putative Role ◽  
Telomere Capping ◽  
Chromosome Fusions ◽  
Deficient Mice

ABSTRACT The homologous recombination (HR) DNA repair pathway participates in telomere length maintenance in yeast but its putative role at mammalian telomeres is unknown. Mammalian Rad54 is part of the HR machinery, and Rad54-deficient mice show a reduced HR capability. Here, we show that Rad54-deficient mice also show significantly shorter telomeres than wild-type controls, indicating that Rad54 activity plays an essential role in telomere length maintenance in mammals. Rad54 deficiency also resulted in an increased frequency of end-to-end chromosome fusions involving telomeres compared to the controls, suggesting a putative role of Rad54 in telomere capping. Finally, the study of mice doubly deficient for Rad54 and DNA-PKcs showed that telomere fusions due to DNA-PKcs deficiency were not rescued in the absence of Rad54, suggesting that they are not mediated by Rad54 activity.

scholarly journals Understanding the mechanism of monoADP ribosylation in OsSRT1 and its linkage to the DNA repair system under stress conditions

2021 ◽  
Author(s):  
Nilabhra Mitra ◽  
Sanghamitra Dey
Keyword(s):  
Dna Repair ◽  
Abiotic Stress ◽  
Stress Conditions ◽  
Repair System ◽  
Repair Pathway ◽  
Natural Plant ◽  
Plant Polyphenol ◽  
Negative Effect ◽  
Strong Activator

The role of sirtuins in plants are slowly unraveling. There are only reports of H3K9Ac deacetylation by OsSRT1. Here our studies shade light on its dual enzyme capability with preference for mono ADP ribosylation over deacetylation. OsSRT1 can specifically transfer the single ADP ribose group on its substrates in an enzymatic manner. This mono ADPr effect is not well known in plants, more so for deacetylases. The products of this reaction (NAM and ADP ribose) have immense negative effect on this enzyme suggesting a tighter regulation. Resveratrol, a natural plant polyphenol proves to be a strong activator of this enzyme at 150 μM concentration. Under different abiotic stress conditions, we could link this ADP ribosylase activity to the DNA repair pathway by activating the enzyme PARP1. Metal stress in plants also influences these enzyme activities.

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 XPC promotes MDM2-mediated degradation of the p53 tumor suppressor

2014 ◽  
Vol 25 (2) ◽  
pp. 213-221 ◽  
Author(s):  
Jing Yan Krzeszinski ◽  
Vitnary Choe ◽  
Jia Shao ◽  
Xin Bao ◽  
Haili Cheng ◽  
...  
Keyword(s):  
Dna Repair ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Uv Irradiation ◽  
Binding Protein ◽  
P53 Protein ◽  
Critical Role ◽  
Direct Interaction ◽  
Degradation Pathway

Although ubiquitin receptor Rad23 has been implicated in bringing ubiquitylated p53 to the proteasome, how Rad23 recognizes p53 remains unclear. We demonstrate that XPC, a Rad23-binding protein, regulates p53 turnover. p53 protein in XPC-deficient cells remains ubiquitylated, but its association with the proteasome is drastically reduced, indicating that XPC regulates a postubiquitylation event. Furthermore, we found that XPC participates in the MDM2-mediated p53 degradation pathway via direct interaction with MDM2. XPC W690S pathogenic mutant is specifically defective for MDM2 binding and p53 degradation. p53 is known to become stabilized following UV irradiation but can be rendered unstable by XPC overexpression, underscoring a critical role of XPC in p53 regulation. Elucidation of the proteolytic role of XPC in cancer cells will help to unravel the detailed mechanisms underlying the coordination of DNA repair and proteolysis.

Role of Telomeric TRF2 in Orosphere Formation and CSC Phenotype Maintenance Through Efficient DNA Repair Pathway and its Correlation with Recurrence in OSCC

2018 ◽  
Vol 14 (6) ◽  
pp. 871-887 ◽  
Author(s):  
Arka Saha ◽  
Souvick Roy ◽  
Madhabananda Kar ◽  
Shomereeta Roy ◽  
Shweta Thakur ◽  
...  
Keyword(s):  
Dna Repair ◽  
Repair Pathway

scholarly journals DNA-PKcs phosphorylation at the T2609 cluster alters the repair pathway choice during immunoglobulin class switch recombination

2020 ◽  
Author(s):  
Jennifer L. Crowe ◽  
Xiaobin S. Wang ◽  
Zhengping Shao ◽  
Brian J. Lee ◽  
Verna Estes ◽  
...  
Keyword(s):  
Dna Repair ◽  
B Cells ◽  
Class Switch Recombination ◽  
Chromosomal Translocation ◽  
Radiation Sensitivity ◽  
Repair Pathway ◽  
End Joining ◽  
Class Switch ◽  
Pathway Choice

AbstractThe DNA-dependent protein kinase (DNA-PK), composed of the KU heterodimer and the large catalytic subunit (DNA-PKcs), is a classical non-homologous end-joining (cNHEJ) factor. Naïve B cells undergo class switch recombination (CSR) to generate antibodies with different isotypes by joining two DNA double-strand breaks at different switching regions via the cNHEJ pathway. DNA-PK and the cNHEJ pathway play important roles in the DNA repair phase of CSR. To initiate cNHEJ, KU binds to DNA ends, and recruits and activates DNA-PK. DNA-PKcs is the best-characterized substrate of DNA-PK, which phosphorylates DNA-PKcs at both the S2056 and T2609 clusters. Loss of T2609 cluster phosphorylation increases radiation sensitivity, suggesting a role of T2609 phosphorylation in DNA repair. Using the DNA-PKcs5A mouse model carrying an alanine substitution at the T2609 cluster, here we show that loss of T2609 phosphorylation of DNA-PKcs does not affect the CSR efficiency. Yet, the CSR junctions recovered from DNA-PKcs5A/5A B cells reveal increased chromosomal translocation, excess end-resection, and preferential usage of micro-homology – all signs of the alternative end-joining pathway. Thus, these results uncover a role of DNA-PKcs T2609 phosphorylation in promoting cNHEJ repair pathway choice during CSR.Key pointsLoss of T2069 cluster phosphorylation of DNA-PKcs promotes Alt-EJ-mediated CSR.

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