Werner syndrome protein, the MRE11 complex and ATR: menage-à-trois in guarding genome stability during DNA replication?

BioEssays ◽  
2004 ◽  
Vol 26 (3) ◽  
pp. 306-313 ◽  
Author(s):  
Pietro Pichierri ◽  
Annapaola Franchitto
Keyword(s):  
Dna Replication ◽  
Genome Stability ◽  
Werner Syndrome ◽  
Mre11 Complex ◽  
Werner Syndrome Protein ◽  
Syndrome Protein

scholarly journals Werner Syndrome Protein and DNA Replication

2018 ◽  
Vol 19 (11) ◽  
pp. 3442 ◽  
Author(s):  
Shibani Mukherjee ◽  
Debapriya Sinha ◽  
Souparno Bhattacharya ◽  
Kalayarasan Srinivasan ◽  
Salim Abdisalaam ◽  
...  
Keyword(s):  
Dna Replication ◽  
Ataxia Telangiectasia ◽  
Replication Fork ◽  
Genome Stability ◽  
Werner Syndrome ◽  
Genotoxic Stress ◽  
Premature Aging ◽  
Replication Forks ◽  
Werner Syndrome Protein ◽  
Syndrome Protein

Werner Syndrome (WS) is an autosomal recessive disorder characterized by the premature development of aging features. Individuals with WS also have a greater predisposition to rare cancers that are mesenchymal in origin. Werner Syndrome Protein (WRN), the protein mutated in WS, is unique among RecQ family proteins in that it possesses exonuclease and 3′ to 5′ helicase activities. WRN forms dynamic sub-complexes with different factors involved in DNA replication, recombination and repair. WRN binding partners either facilitate its DNA metabolic activities or utilize it to execute their specific functions. Furthermore, WRN is phosphorylated by multiple kinases, including Ataxia telangiectasia mutated, Ataxia telangiectasia and Rad3 related, c-Abl, Cyclin-dependent kinase 1 and DNA-dependent protein kinase catalytic subunit, in response to genotoxic stress. These post-translational modifications are critical for WRN to function properly in DNA repair, replication and recombination. Accumulating evidence suggests that WRN plays a crucial role in one or more genome stability maintenance pathways, through which it suppresses cancer and premature aging. Among its many functions, WRN helps in replication fork progression, facilitates the repair of stalled replication forks and DNA double-strand breaks associated with replication forks, and blocks nuclease-mediated excessive processing of replication forks. In this review, we specifically focus on human WRN’s contribution to replication fork processing for maintaining genome stability and suppressing premature aging. Understanding WRN’s molecular role in timely and faithful DNA replication will further advance our understanding of the pathophysiology of WS.

scholarly journals The Werner syndrome protein: linking the replication checkpoint response to genome stability

Aging ◽  
2011 ◽  
Vol 3 (3) ◽  
pp. 311-318 ◽  
Author(s):  
Pietro Pichierri ◽  
Francesca Ammazzalorso ◽  
Margherita Bignami ◽  
Annapaola Franchitto
Keyword(s):  
Genome Stability ◽  
Werner Syndrome ◽  
Replication Checkpoint ◽  
Checkpoint Response ◽  
Werner Syndrome Protein ◽  
Syndrome Protein

scholarly journals Linkage between Werner Syndrome Protein and the Mre11 Complex via Nbs1

2004 ◽  
Vol 279 (20) ◽  
pp. 21169-21176 ◽  
Author(s):  
Wen-Hsing Cheng ◽  
Cayetano von Kobbe ◽  
Patricia L. Opresko ◽  
L. Matthew Arthur ◽  
Kenshi Komatsu ◽  
...  
Keyword(s):  
Werner Syndrome ◽  
Mre11 Complex ◽  
Werner Syndrome Protein ◽  
Syndrome Protein
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