Deciphering the mechanism of processive ssDNA digestion by the Dna2-RPA ensemble

Jiangchuan Shen, Yiling Zhao, Nhung Tuyet Pham, Yuxi Li, Yixiang Zhang, Jonathan Trinidad, Grzegorz Ira, Zhi Qi () and Hengyao Niu ()
Additional contact information
Jiangchuan Shen: Indiana University
Yiling Zhao: Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University
Nhung Tuyet Pham: Baylor College of Medicine
Yuxi Li: Indiana University
Yixiang Zhang: Biological Mass Spectrometry Facility, Indiana University
Jonathan Trinidad: Biological Mass Spectrometry Facility, Indiana University
Grzegorz Ira: Baylor College of Medicine
Zhi Qi: Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University
Hengyao Niu: Indiana University

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Single-stranded DNA (ssDNA) commonly occurs as intermediates in DNA metabolic pathways. The ssDNA binding protein, RPA, not only protects the integrity of ssDNA, but also directs the downstream factor that signals or repairs the ssDNA intermediate. However, it remains unclear how these enzymes/factors outcompete RPA to access ssDNA. Using the budding yeast Saccharomyces cerevisiae as a model system, we find that Dna2 — a key nuclease in DNA replication and repair — employs a bimodal interface to act with RPA both in cis and in trans. The cis-activity makes RPA a processive unit for Dna2-catalyzed ssDNA digestion, where RPA delivers its bound ssDNA to Dna2. On the other hand, activity in trans is mediated by an acidic patch on Dna2, which enables it to function with a sub-optimal amount of RPA, or to overcome DNA secondary structures. The trans-activity mode is not required for cell viability, but is necessary for effective double strand break (DSB) repair.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-27940-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27940-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-27940-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().