scholarly journals Emerging Roles of RAD52 in Genome Maintenance

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1038 ◽  
Author(s):  
Manisha Jalan ◽  
Kyrie S. Olsen ◽  
Simon N. Powell
Keyword(s):  
Genome Stability ◽  
Genome Integrity ◽  
Repair Pathway ◽  
Genome Maintenance ◽  
Knock Out ◽  
Repair Protein ◽  
Attractive Therapeutic Target ◽  
Dna Repair Protein ◽  
Synthetically Lethal ◽  
Knock Out Mice

The maintenance of genome integrity is critical for cell survival. Homologous recombination (HR) is considered the major error-free repair pathway in combatting endogenously generated double-stranded lesions in DNA. Nevertheless, a number of alternative repair pathways have been described as protectors of genome stability, especially in HR-deficient cells. One of the factors that appears to have a role in many of these pathways is human RAD52, a DNA repair protein that was previously considered to be dispensable due to a lack of an observable phenotype in knock-out mice. In later studies, RAD52 deficiency has been shown to be synthetically lethal with defects in BRCA genes, making RAD52 an attractive therapeutic target, particularly in the context of BRCA-deficient tumors.

scholarly journals A DNA repair protein and histone methyltransferase interact to promote genome stability in the Caenorhabditis elegans germ line

PLoS Genetics ◽  
2019 ◽  
Vol 15 (2) ◽  
pp. e1007992 ◽  
Author(s):  
Bing Yang ◽  
Xia Xu ◽  
Logan Russell ◽  
Matthew T. Sullenberger ◽  
Judith L. Yanowitz ◽  
...  
Keyword(s):  
Dna Repair ◽  
Caenorhabditis Elegans ◽  
Genome Stability ◽  
Germ Line ◽  
Histone Methyltransferase ◽  
Repair Protein ◽  
Dna Repair Protein

scholarly journals The DNA repair protein NBS1 influences the base excision repair pathway

2009 ◽  
Vol 30 (3) ◽  
pp. 408-415 ◽  
Author(s):  
D. Sagan ◽  
R. Muller ◽  
C. Kroger ◽  
A. Hematulin ◽  
S. Mortl ◽  
...  
Keyword(s):  
Dna Repair ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Repair Pathway ◽  
Base Excision Repair Pathway ◽  
Repair Protein ◽  
Dna Repair Protein ◽  
Base Excision

scholarly journals The yeast core spliceosome maintains genome integrity through R-loop prevention and α-tubulin expression

2018 ◽  
Author(s):  
Annie S. Tam ◽  
Veena Mathew ◽  
Tianna S. Sihota ◽  
Anni Zhang ◽  
Peter C. Stirling
Keyword(s):  
Gene Expression ◽  
Dna Replication ◽  
Chromosome Segregation ◽  
Genome Stability ◽  
Spindle Assembly Checkpoint ◽  
Genome Instability ◽  
Genome Integrity ◽  
Genome Maintenance ◽  
Maintenance Factors ◽  
Spindle Assembly Checkpoint Protein

To achieve genome stability cells must coordinate the action of various DNA transactions including DNA replication, repair, transcription and chromosome segregation. How transcription and RNA processing enable genome stability is only partly understood. Two predominant models have emerged: one involving changes in gene expression that perturb other genome maintenance factors, and another in which genotoxic DNA:RNA hybrids, called R-loops, impair DNA replication. Here we characterize genome instability phenotypes in a panel yeast splicing factor mutants and find that mitotic defects, and in some cases R-loop accumulation, are causes of genome instability. Genome instability in splicing mutants is exacerbated by loss of the spindle-assembly checkpoint protein Mad1. Moreover, removal of the intron from the α-tubulin gene TUB1 restores genome integrity. Thus, while R-loops contribute in some settings, defects in yeast splicing predominantly lead to genome instability through effects on gene expression.

scholarly journals CtIP is essential for telomere replication

2019 ◽  
Vol 47 (17) ◽  
pp. 8927-8940 ◽  
Author(s):  
Susanna Stroik ◽  
Kevin Kurtz ◽  
Eric A Hendrickson
Keyword(s):  
Dna Repair ◽  
Genome Stability ◽  
Telomere Dysfunction ◽  
Replication Forks ◽  
Telomeric Dna ◽  
Telomere Shortening ◽  
Repair Protein ◽  
Dna Repair Protein ◽  
Telomere Replication ◽  
Human Telomere

Abstract The maintenance of telomere length is critical to longevity and survival. Specifically, the failure to properly replicate, resect, and/or form appropriate telomeric structures drives telomere shortening and, in turn, genomic instability. The endonuclease CtIP is a DNA repair protein that is well-known to promote genome stability through the resection of endogenous DNA double-stranded breaks. Here, we describe a novel role for CtIP. We show that in the absence of CtIP, human telomeres shorten rapidly to non-viable lengths. This telomere dysfunction results in an accumulation of fusions, breaks, and frank telomere loss. Additionally, CtIP suppresses the generation of circular, extrachromosomal telomeric DNA. These latter structures appear to arise from arrested DNA replication forks that accumulate in the absence of CtIP. Hence, CtIP is required for faithful replication through telomeres via its roles at stalled replication tracts. Our findings demonstrate a new role for CtIP as a protector of human telomere integrity.

scholarly journals Ubiquitin ligase UBR3 regulates cellular levels of the essential DNA repair protein APE1 and is required for genome stability

2011 ◽  
Vol 40 (2) ◽  
pp. 701-711 ◽  
Author(s):  
Cornelia Meisenberg ◽  
Phillip S. Tait ◽  
Irina I. Dianova ◽  
Katherine Wright ◽  
Mariola J. Edelmann ◽  
...  
Keyword(s):  
Dna Repair ◽  
Ubiquitin Ligase ◽  
Genome Stability ◽  
Repair Protein ◽  
Dna Repair Protein

scholarly journals A Uve1p-Mediated Mismatch Repair Pathway inSchizosaccharomyces pombe

1999 ◽  
Vol 19 (7) ◽  
pp. 4703-4710 ◽  
Author(s):  
Balveen Kaur ◽  
J. Lee A. Fraser ◽  
Greg A. Freyer ◽  
Scott Davey ◽  
Paul W. Doetsch
Keyword(s):  
Dna Repair ◽  
Mismatch Repair ◽  
Excision Repair ◽  
Uv Light ◽  
Initial Step ◽  
Biochemical Properties ◽  
Repair Pathway ◽  
Repair Protein ◽  
Specific Manner ◽  
Dna Repair Protein

ABSTRACT UV damage endonuclease (Uve1p) from Schizosaccharomyces pombe was initially described as a DNA repair enzyme specific for the repair of UV light-induced photoproducts and proposed as the initial step in an alternative excision repair pathway. Here we present biochemical and genetic evidence demonstrating that Uve1p is also a mismatch repair endonuclease which recognizes and cleaves DNA 5′ to the mispaired base in a strand-specific manner. The biochemical properties of the Uve1p-mediated mismatch endonuclease activity are similar to those of the Uve1p-mediated UV photoproduct endonuclease. Mutants lacking Uve1p display a spontaneous mutator phenotype, further confirming the notion that Uve1p plays a role in mismatch repair. These results suggest that Uve1p has a surprisingly broad substrate specificity and may function as a general type of DNA repair protein with the capacity to initiate mismatch repair in certain organisms.

scholarly journals Role of Histone Methylation in Maintenance of Genome Integrity

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1000
Author(s):  
Arjamand Mushtaq ◽  
Ulfat Syed Mir ◽  
Clayton R. Hunt ◽  
Shruti Pandita ◽  
Wajahat W. Tantray ◽  
...  
Keyword(s):  
Dna Damage ◽  
Histone Methylation ◽  
Genomic Stability ◽  
Genome Integrity ◽  
Repair Pathway ◽  
Post Translational Modifications ◽  
Damage Repair ◽  
Repair Protein ◽  
Cellular Pathways

: Packaging of the eukaryotic genome with histone and other proteins forms a chromatin structure that regulates the outcome of all DNA mediated processes. The cellular pathways that ensure genomic stability detect and repair DNA damage through mechanisms that are critically dependent upon chromatin structures established by histones and, particularly upon transient histone post-translational modifications. Though subjected to a range of modifications, histone methylation is especially crucial for DNA damage repair, as the methylated histones often form platforms for subsequent repair protein binding at damaged sites. In this review, we highlight and discuss how histone methylation impacts the maintenance of genome integrity through effects related to DNA repair and repair pathway choice.

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