Fidelity of DNA Polymerase δ Holoenzyme fromSaccharomyces cerevisiae:  The Sliding Clamp Proliferating Cell Nuclear Antigen Decreases Its Fidelity†

Biochemistry ◽  
2003 ◽  
Vol 42 (48) ◽  
pp. 14207-14213 ◽  
Author(s):  
Keiji Hashimoto ◽  
Kikuo Shimizu ◽  
Naomi Nakashima ◽  
Akio Sugino
2003 ◽  
Vol 278 (12) ◽  
pp. 10041-10047 ◽  
Author(s):  
Li Liu ◽  
Esther M. Rodriguez-Belmonte ◽  
Nayef Mazloum ◽  
Bin Xie ◽  
Marietta Y. W. T. Lee

1989 ◽  
Vol 17 (5) ◽  
pp. 1805-1821 ◽  
Author(s):  
Federico Focher ◽  
Max Gassmann ◽  
Peter Hafkmeyer ◽  
Elena Ferrari ◽  
Silvio Spadari ◽  
...  

1996 ◽  
Vol 271 (49) ◽  
pp. 31711-31717 ◽  
Author(s):  
Dmitry Ju. Mozzherin ◽  
Maeve McConnell ◽  
Maxim V. Jasko ◽  
Alexander A. Krayevsky ◽  
Cheng-Keat Tan ◽  
...  

2016 ◽  
Vol 113 (13) ◽  
pp. E1777-E1786 ◽  
Author(s):  
Mark Hedglin ◽  
Binod Pandey ◽  
Stephen J. Benkovic

In eukaryotes, DNA polymerase δ (pol δ) is responsible for replicating the lagging strand template and anchors to the proliferating cell nuclear antigen (PCNA) sliding clamp to form a holoenzyme. The stability of this complex is integral to every aspect of lagging strand replication. Most of our understanding comes fromSaccharomyces cerevisaewhere the extreme stability of the pol δ holoenzyme ensures that every nucleobase within an Okazaki fragment is faithfully duplicated before dissociation but also necessitates an active displacement mechanism for polymerase recycling and exchange. However, the stability of the human pol δ holoenzyme is unknown. We designed unique kinetic assays to analyze the processivity and stability of the pol δ holoenzyme. Surprisingly, the results indicate that human pol δ maintains a loose association with PCNA while replicating DNA. Such behavior has profound implications on Okazaki fragment synthesis in humans as it limits the processivity of pol δ on undamaged DNA and promotes the rapid dissociation of pol δ from PCNA on stalling at a DNA lesion.


2002 ◽  
Vol 277 (27) ◽  
pp. 24340-24345 ◽  
Author(s):  
Xiaoqing Lu ◽  
Cheng-Keat Tan ◽  
Jin-Qiu Zhou ◽  
Min You ◽  
L. Michael Carastro ◽  
...  

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