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T7 replisome directly overcomes DNA damage

Cornell Affiliated Author(s)

Author

B. Sun
M. Pandey
J.T. Inman
Y. Yang
M. Kashlev
S.S. Patel
M.D. Wang

Abstract

Cells and viruses possess several known 'restart' pathways to overcome lesions during DNA replication. However, these 'bypass' pathways leave a gap in replicated DNA or require recruitment of accessory proteins, resulting in significant delays to fork movement or even cell division arrest. Using single-molecule and ensemble methods, we demonstrate that the bacteriophage T7 replisome is able to directly replicate through a leading-strand cyclobutane pyrimidine dimer (CPD) lesion. We show that when a replisome encounters the lesion, a substantial fraction of DNA polymerase (DNAP) and helicase stay together at the lesion, the replisome does not dissociate and the helicase does not move forward on its own. The DNAP is able to directly replicate through the lesion by working in conjunction with helicase through specific helicase-DNAP interactions. These observations suggest that the T7 replisome is fundamentally permissive of DNA lesions via pathways that do not require fork adjustment or replisome reassembly.

Date Published

Journal

Nature Communications

Volume

6

URL

https://www.scopus.com/inward/record.uri?eid=2-s2.0-84950268197&doi=10.1038%2fncomms10260&partnerID=40&md5=277a8a404ccdf9ded7c00fe0872e7288

DOI

10.1038/ncomms10260

Research Area

Group (Lab)

Michelle Wang Group

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