Mystery of Expansion: DNA Metabolism and Unstable Repeats

Author(s):  
Irina V. Grishchenko ◽  
Yana V. Purvinsh ◽  
Dmitry V. Yudkin
Keyword(s):  
Genetics ◽  
1981 ◽  
Vol 97 (3-4) ◽  
pp. 607-623 ◽  
Author(s):  
J B Boyd ◽  
M D Golino ◽  
K E S Shaw ◽  
C J Osgood ◽  
M M Green

ABSTRACT A total of 34 third chromosomes of Drosophila melanogaster that render homozygous larvae hypersensitive to killing by chemical mutagens have been isolated. Genetic analyses have placed responsible mutations in more than eleven complementation groups. Mutants in three complementation groups are strongly sensitive to methyl methanesulfonate, those in one are sensitive to nitrogen mustard, and mutants in six groups are hypersensitive to both mutagens. Eight of the ten loci mapped fall within 15% of the genetic map that encompasses the centromere of chromosome 3. Mutants from four of the complementation groups are associated with moderate to strong meiotic effects in females. Preliminary biochemical analyses have implicated seven of these loci in DNA metabolism.


Genetics ◽  
1998 ◽  
Vol 148 (3) ◽  
pp. 1055-1067
Author(s):  
Steven D Harris ◽  
Peter R Kraus

Abstract In Aspergillus nidulans, germinating conidia undergo multiple rounds of nuclear division before the formation of the first septum. Previous characterization of temperature-sensitive sepB and sepJ mutations showed that although they block septation, they also cause moderate defects in chromosomal DNA metabolism. Results presented here demonstrate that a variety of other perturbations of chromosomal DNA metabolism also delay septum formation, suggesting that this is a general cellular response to the presence of sublethal DNA damage. Genetic evidence is provided that suggests that high levels of cyclin-dependent kinase (cdk) activity are required for septation in A. nidulans. Consistent with this notion, the inhibition of septum formation triggered by defects in chromosomal DNA metabolism depends upon Tyr-15 phosphorylation of the mitotic cdk p34nimX. Moreover, this response also requires elements of the DNA damage checkpoint pathway. A model is proposed that suggests that the DNA damage checkpoint response represents one of multiple sensory inputs that modulates p34nimX activity to control the timing of septum formation.


Genetics ◽  
2001 ◽  
Vol 159 (4) ◽  
pp. 1511-1525 ◽  
Author(s):  
Teresa de los Santos ◽  
Josef Loidl ◽  
Brittany Larkin ◽  
Nancy M Hollingsworth

Abstract The MMS4 gene of Saccharomyces cerevisiae was originally identified due to its sensitivity to MMS in vegetative cells. Subsequent studies have confirmed a role for MMS4 in DNA metabolism of vegetative cells. In addition, mms4 diploids were observed to sporulate poorly. This work demonstrates that the mms4 sporulation defect is due to triggering of the meiotic recombination checkpoint. Genetic, physical, and cytological analyses suggest that MMS4 functions after the single end invasion step of meiotic recombination. In spo13 diploids, red1, but not mek1, is epistatic to mms4 for sporulation and spore viability, suggesting that MMS4 may be required only when homologs are capable of undergoing synapsis. MMS4 and MUS81 are in the same epistasis group for spore viability, consistent with biochemical data that show that the two proteins function in a complex. In contrast, MMS4 functions independently of MSH5 in the production of viable spores. We propose that MMS4 is required for the processing of specific recombination intermediates during meiosis.


Genetics ◽  
1985 ◽  
Vol 110 (3) ◽  
pp. 381-395
Author(s):  
Leland H Hartwell ◽  
David Smith

ABSTRACT Thirteen of 14 temperature-sensitive mutants deficient in successive steps of mitotic chromosome transmission (cdc2, 4, 5, 6, 7, 8, 9, 13, 14, 15, 16, 17 and 20) from spindle pole body separation to a late stage of nuclear division exhibited a dramatic increase in the frequency of chromosome loss and/or mitotic recombination when they were grown at their maximum permissive temperatures. The increase in chromosome loss and/or recombination is likely to be due to the deficiency of functional gene product rather than to an aberrant function of the mutant gene product since the mutant alleles are, with one exception, recessive to the wild-type allele for this phenotype. The generality of this result suggests that a delay in almost any stage of chromosome replication or segregation leads to a decrease in the fidelity of mitotic chromosome transmission. In contrast, temperature-sensitive mutants defective in the control step of the cell cycle (cdc28), in cytokinesis (cdc3) or in protein synthesis (ils1) did not exhibit increased recombination or chromosome loss.—Based upon previous results with mutants and DNA-damaging agents in a variety of organisms, we suggest that the induction of mitotic recombination in certain mutants is due to the action of a repair pathway upon nicks or gaps left in the DNA. This interpretation is supported by the fact that the induced recombination is dependent upon the RAD52 gene product, an essential component in the recombinogenic DNA repair pathway. Gene products whose deficiency leads to induced recombination are, therefore, strong candidates for proteins that function in DNA metabolism. Among the mutants that induce recombination are those known to be defective in some aspect of DNA replication (cdc2, 6, 8, 9) as well as some mutants defective in the G2 (cdc13 and 17) and M (cdc5 and 14) phases of the mitotic cycle. We suggest that special aspects of DNA metabolism may be occurring in G2 and M in order to prepare the chromosomes for proper segregation.


1969 ◽  
Vol 38 (1) ◽  
pp. 795-840 ◽  
Author(s):  
C C Richardson
Keyword(s):  

DNA Repair ◽  
2010 ◽  
Vol 9 (5) ◽  
pp. 567-578 ◽  
Author(s):  
Nicolas Siaud ◽  
Emeline Dubois ◽  
Sophie Massot ◽  
Aurélien Richaud ◽  
Eloïse Dray ◽  
...  
Keyword(s):  

2021 ◽  
Author(s):  
Qiaochu Wei ◽  
Jiming Shen ◽  
Dongni Wang ◽  
Xu Han ◽  
Jing Shi ◽  
...  

Abstract Background: Flap endonuclease 1 (FEN1) is a structure-specific nuclease that plays a role in a variety of DNA metabolism processes. FEN1 is important for maintaining genomic stability and regulating cell growth and development. It is associated with the occurrence and development of several diseases, especially cancers. There is a lack of systematic bibliometric analyses focusing on research trends and knowledge structures related to FEN1.Purpose: To analyze hotspots, the current state and research frontiers performed for FEN1 over the past 15 years. Methods: Publications were retrieved from the Web of Science Core Collection (WoSCC) database, analyzing publication dates ranging from 2005 to 2019. VOSviewer1.6.15 and Citespace5.7 R1 were used to perform a bibliometric analysis in terms of countries, institutions, authors, journals and research areas related to FEN1. A total of 421 publications were included in this analysis. Results: Our findings indicated that FEN1 has received more attention and interest from researchers in the past 15 years. Institutes in the United States, specifically the Beckman Research Institute of City of Hope published the most research related to FEN1. SHEN BH,ZHENG L and BAMBARA RA were the most active researchers investigating this endonuclease and most of this research was published in the Journal of Biological Chemistry. The main scientific areas of FEN1 were related to biochemistry, molecular biology,cell biology,genetics and oncology. Research hotspots included biological activities, DNA metabolism mechanisms, protein-protein interactions and gene mutations. Research frontiers included oxidative stress, phosphorylation and tumor progression and treatment. Conclusion: This bibliometric study may aid researchers in the understanding of the knowledge base and research frontiers associated with FEN1. In addition, emerging hotspots for research can be used as the subjects of future studies.


1998 ◽  
Vol 5 ◽  
pp. 141
Author(s):  
B.G. Borzenko ◽  
O.A. Verkhova ◽  
Z.M. Skorobogatova ◽  
T.G. Skorobogataya ◽  
T.A. Shvetz ◽  
...  

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