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Switch-like control of helicase processivity by single-stranded DNA binding protein
Journal article   Open access   Peer reviewed

Switch-like control of helicase processivity by single-stranded DNA binding protein

Barbara Stekas, Steve Yeo, Alice Troitskaia, Masayoshi Honda, Sei Sho, Maria Spies and Yann R Chemla
eLife, Vol.10, e60515
03/19/2021
DOI: 10.7554/eLife.60515
PMCID: PMC7997660
PMID: 33739282
url
https://doi.org/10.7554/eLife.60515View
Published (Version of record) Open Access

Abstract

Helicases utilize nucleotide triphosphate (NTP) hydrolysis to translocate along single-stranded nucleic acids (NA) and unwind the duplex. In the cell, helicases function in the context of other NA-associated proteins such as single-stranded DNA binding proteins. Such encounters regulate helicase function, although the underlying mechanisms remain largely unknown. Ferroplasma acidarmanus xeroderma pigmentosum group D (XPD) helicase serves as a model for understanding the molecular mechanisms of superfamily 2B helicases, and its activity is enhanced by the cognate single-stranded DNA binding protein replication protein A 2 (RPA2). Here, optical trap measurements of the unwinding activity of a single XPD helicase in the presence of RPA2 reveal a mechanism in which XPD interconverts between two states with different processivities and transient RPA2 interactions stabilize the more processive state, activating a latent ‘processivity switch’ in XPD. A point mutation at a regulatory DNA binding site on XPD similarly activates this switch. These findings provide new insights on mechanisms of helicase regulation by accessory proteins.

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