scholarly journals Human premature aging, DNA repair and RecQ helicases

2007 ◽  
Vol 35 (22) ◽  
pp. 7527-7544 ◽  
Author(s):  
R. M. Brosh ◽  
V. A. Bohr
Keyword(s):  
Dna Repair ◽  
Premature Aging ◽  
Recq Helicases

DNA Repair and Transcription in Human Premature Aging Disorders

1998 ◽  
Vol 3 (1) ◽  
pp. 11-13 ◽  
Author(s):  
Vilhelm A Bohr ◽  
Grigoiy Dianov ◽  
Adayabalam Balajee ◽  
Alfred May ◽  
David K Orren
Keyword(s):  
Dna Repair ◽  
Premature Aging

scholarly journals RecQ helicases: suppressors of tumorigenesis and premature aging

2003 ◽  
Vol 374 (3) ◽  
pp. 577-606 ◽  
Author(s):  
Csanád Z. BACHRATI ◽  
Ian D. HICKSON
Keyword(s):  
Replication Fork ◽  
Germ Line ◽  
Genetic Disorders ◽  
Premature Aging ◽  
Recq Helicase ◽  
Dna Helicases ◽  
Recq Helicases ◽  
Protein Partners ◽  
Line Defects ◽  
Rothmund Thomson Syndrome

The RecQ helicases represent a subfamily of DNA helicases that are highly conserved in evolution. Loss of RecQ helicase function leads to a breakdown in the maintenance of genome integrity, in particular hyper-recombination. Germ-line defects in three of the five known human RecQ helicases give rise to defined genetic disorders associated with cancer predisposition and/or premature aging. These are Bloom's syndrome, Werner's syndrome and Rothmund–Thomson syndrome, which are caused by defects in the genes BLM, WRN and RECQ4 respectively. Here we review the properties of RecQ helicases in organisms from bacteria to humans, with an emphasis on the biochemical functions of these enzymes and the range of protein partners that they operate with. We will discuss models in which RecQ helicases are required to protect against replication fork demise, either through prevention of fork breakdown or restoration of productive DNA synthesis.

Skin Abnormalities in Disorders with DNA Repair Defects, Premature Aging, and Mitochondrial Dysfunction

2021 ◽  
Author(s):  
Mansoor Hussain ◽  
Sudarshan Krishnamurthy ◽  
Jaimin Patel ◽  
Edward Kim ◽  
Beverly A. Baptiste ◽  
...  
Keyword(s):  
Dna Repair ◽  
Mitochondrial Dysfunction ◽  
Premature Aging ◽  
Skin Abnormalities

scholarly journals RecQ helicases in DNA repair and cancer targets

2020 ◽  
Vol 64 (5) ◽  
pp. 819-830
Author(s):  
Joseph A. Newman ◽  
Opher Gileadi
Keyword(s):  
Dna Repair ◽  
Small Molecules ◽  
Atp Hydrolysis ◽  
Cancer Therapeutics ◽  
Genome Integrity ◽  
Mechanistic Study ◽  
Synthetic Lethal ◽  
Recq Helicases ◽  
Repair Pathways ◽  
Higher Eukaryotes

Abstract Helicases are enzymes that use the energy derived from ATP hydrolysis to catalyze the unwinding of DNA or RNA. The RecQ family of helicases is conserved through evolution from prokaryotes to higher eukaryotes and plays important roles in various DNA repair pathways, contributing to the maintenance of genome integrity. Despite their roles as general tumor suppressors, there is now considerable interest in exploiting RecQ helicases as synthetic lethal targets for the development of new cancer therapeutics. In this review, we summarize the latest developments in the structural and mechanistic study of RecQ helicases and discuss their roles in various DNA repair pathways. Finally, we consider the potential to exploit RecQ helicases as therapeutic targets and review the recent progress towards the development of small molecules targeting RecQ helicases as cancer therapeutics.

scholarly journals The ATPase Domain but Not the Acidic Region of Cockayne Syndrome Group B Gene Product Is Essential for DNA Repair

1999 ◽  
Vol 10 (11) ◽  
pp. 3583-3594 ◽  
Author(s):  
Robert M. Brosh ◽  
Adayabalam S. Balajee ◽  
Rebecca R. Selzer ◽  
Morten Sunesen ◽  
Luca Proietti De Santis ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Excision Repair ◽  
Uv Light ◽  
Genetic Disorder ◽  
Cockayne Syndrome ◽  
Premature Aging ◽  
Atpase Domain ◽  
Acidic Region

Cockayne syndrome (CS) is a human genetic disorder characterized by UV sensitivity, developmental abnormalities, and premature aging. Two of the genes involved, CSA andCSB, are required for transcription-coupled repair (TCR), a subpathway of nucleotide excision repair that removes certain lesions rapidly and efficiently from the transcribed strand of active genes. CS proteins have also been implicated in the recovery of transcription after certain types of DNA damage such as those lesions induced by UV light. In this study, site-directed mutations have been introduced to the human CSB gene to investigate the functional significance of the conserved ATPase domain and of a highly acidic region of the protein. The CSB mutant alleles were tested for genetic complementation of UV-sensitive phenotypes in the human CS-B homologue of hamster UV61. In addition, theCSB mutant alleles were tested for their ability to complement the sensitivity of UV61 cells to the carcinogen 4-nitroquinoline-1-oxide (4-NQO), which introduces bulky DNA adducts repaired by global genome repair. Point mutation of a highly conserved glutamic acid residue in ATPase motif II abolished the ability of CSB protein to complement the UV-sensitive phenotypes of survival, RNA synthesis recovery, and gene-specific repair. These data indicate that the integrity of the ATPase domain is critical for CSB function in vivo. Likewise, the CSB ATPase point mutant failed to confer cellular resistance to 4-NQO, suggesting that ATP hydrolysis is required for CSB function in a TCR-independent pathway. On the contrary, a large deletion of the acidic region of CSB protein did not impair the genetic function in the processing of either UV- or 4-NQO-induced DNA damage. Thus the acidic region of CSB is likely to be dispensable for DNA repair, whereas the ATPase domain is essential for CSB function in both TCR-dependent and -independent pathways.

scholarly journals Roles of RECQ helicases in recombination based DNA repair, genomic stability and aging

2008 ◽  
Vol 10 (3) ◽  
pp. 235-252 ◽  
Author(s):  
Dharmendra Kumar Singh ◽  
Byungchan Ahn ◽  
Vilhelm A. Bohr
Keyword(s):  
Dna Repair ◽  
Genomic Stability ◽  
Recq Helicases

scholarly journals NRMT1 knockout mice exhibit phenotypes associated with impaired DNA repair and premature aging

2015 ◽  
Vol 146-148 ◽  
pp. 42-52 ◽  
Author(s):  
Lindsay A. Bonsignore ◽  
John G. Tooley ◽  
Patrick M. Van Hoose ◽  
Eugenia Wang ◽  
Alan Cheng ◽  
...  
Keyword(s):  
Dna Repair ◽  
Knockout Mice ◽  
Premature Aging
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