Biochemistry

Crosstalk between repair pathways elicits double-strand breaks in alkylated DNA and implications for the action of temozolomide

1. Robert P Fuchs
2. Asako Isogawa
3. Joao A Paulo
4. Kazumitsu Onizuka
5. Tatsuro Takahashi
6. Ravindra Amunugama
7. Julien P Duxin
8. Shingo Fujii

• Curated by eLife

  Evaluation summary:

  Glioblastomas, like many tumors, consist of a cohort of actively dividing cells and a substantially larger fraction of non-proliferating cells. The standard of care involves the administration of a chemotherapy drug (temozolomide (TMZ)) whose antitumor activity is thought to be dependent on a toxic intermediate produced during DNA replication. In this report, the authors show how this compound is also processed by the interaction of two DNA repair pathways which produce the same intermediate without the requirement for DNA replication. The paper will be of interest to those scientists concerned with the implications of DNA damage and repair for cancer chemotherapy, particularly for tumors as deadly as glioblastoma.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their names with the authors.)

Reviewed by eLife

Structure-guided microbial targeting of antistaphylococcal prodrugs

1. Justin J Miller
2. Ishaan T Shah
3. Jayda Hatten
4. Yasaman Barekatain
5. Elizabeth A Mueller
6. Ahmed M Moustafa
7. Rachel L Edwards
8. Cynthia S Dowd
9. Geoffrey C Hoops
10. R Jeremy Johnson
11. Paul J Planet
12. Florian L Muller
13. Joseph M Jez
14. Audrey R Odom John

• Curated by eLife

  Evaluation Summary:

  This submission reports an approach to identify bacterial specific carboxyesterases that can be exploited to activate prodrugs of antibiotics in Staphylococcus aureus. The main premise is that charged functional groups found in some antibiotics prevent entry of these into bacteria, an effect that can be circumvented through esterification of the antibiotic to allow entry. Thereafter, activation of the antibiotic will occur in the bacterial cytoplasm through hydrolysis by bacterial esterases. This could lead to new antibiotic delivery strategies.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Bipartite binding and partial inhibition links DEPTOR and mTOR in a mutually antagonistic embrace

1. Maren Heimhalt
2. Alex Berndt
3. Jane Wagstaff
4. Madhanagopal Anandapadamanaban
5. Olga Perisic
6. Sarah Maslen
7. Stephen McLaughlin
8. Conny Wing-Heng Yu
9. Glenn R Masson
10. Andreas Boland
11. Xiaodan Ni
12. Keitaro Yamashita
13. Garib N Murshudov
14. Mark Skehel
15. Stefan M Freund
16. Roger L Williams

• Curated by eLife

  Evaluation Summary:

  This study will be of interest to structural biologists, enzymologists, and cell biologists. The kinase complex mTORC1, a master regulator of cell growth, can be inhibited by another protein, DEPTOR. This protein is of general interest for several reasons, including the hope that understanding how DEPTOR works will lead to new strategies for therapeutically tuning mTORC1 activity. This study provides insights into the binding and inhibitory effects of DEPTOR on mTORC1. Solving a few technical questions will improve the work.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Reviewed by eLife

Zinc ²⁺ ion inhibits SARS-CoV-2 main protease and viral replication in vitro

1. Love Panchariya
2. Wajahat Ali Khan
3. Shobhan Kuila
4. Kirtishila Sonkar
5. Sibasis Sahoo
6. Archita Ghoshal
7. Ankit Kumar
8. Dileep Kumar Verma
9. Abdul Hasan
10. Shubhashis Das
11. Jitendra K Thakur
12. Rajkumar Halder
13. Sujatha Sunil
14. Arulandu Arockiasamy

Reviewed by ScreenIT

NMPylation and de-NMPylation of SARS-CoV-2 nsp9 by the NiRAN domain

1. Bing Wang
2. Dmitri Svetlov
3. Irina Artsimovitch

Reviewed by ScreenIT

Tissue-specific targeting of DNA nanodevices in a multicellular living organism

1. Kasturi Chakraborty
2. Palapuravan Anees
3. Sunaina Surana
4. Simona Martin
5. Jihad Aburas
6. Sandrine Moutel
7. Franck Perez
8. Sandhya P Koushika
9. Paschalis Kratsios
10. Yamuna Krishnan

• Curated by eLife

  Evaluation Summary:

  This paper is of interest to anyone who wants to deliver nucleic acids to specific cell types in whole animals. The work provides a new method to target and deliver of nanodevices to specific cell types and intracellular compartments within live animals. It relies on cell types that can be induced to express a transmembrane protein chimera with a newly developed DNA sequence-specific camelid antibody. In general the data appeared to be of high quality and were well controlled, supporting the authors' conclusions. This work could help pave the way for future advancements in the cell-specific delivery of custom-engineered payloads such as dsDNA nanodevices utilized as quantitative chemosensors and effectors in living cells.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Cellular Activities of SARS-CoV-2 Main Protease Inhibitors Reveal Their Unique Characteristics

1. Wenyue Cao
2. Chia-Chuan Dean Cho
3. Zhi Zachary Geng
4. Xinyu R. Ma
5. Robert Allen
6. Namir Shaabani
7. Erol C. Vatansever
8. Yugendar R. Alugubelli
9. Yuying Ma
10. William H. Ellenburg
11. Kai S. Yang
12. Yuchen Qiao
13. Henry Ji
14. Shiqing Xu
15. Wenshe Ray Liu

Reviewed by ScreenIT

The fatty acid site is coupled to functional motifs in the SARS-CoV-2 spike protein and modulates spike allosteric behaviour

1. A. Sofia F. Oliveira
2. Deborah K. Shoemark
3. Amaurys Avila Ibarra
4. Andrew D. Davidson
5. Imre Berger
6. Christiane Schaffitzel
7. Adrian J. Mulholland

Reviewed by ScreenIT

Structure and mechanistic features of the prokaryotic minimal RNase P

1. Rebecca Feyh
2. Nadine B. Wäber
3. Simone Prinz
4. Pietro Ivan Giammarinaro
5. Gert Bange
6. Georg Hochberg
7. Roland K. Hartmann
8. Florian Altegoer

• Curated by eLife

  Evaluation Summary:

  This manuscript provides the first 3D structure of a novel type of RNA processing enzyme recently identified in bacteria. It convincingly uses cryoEM and biochemistry to describe how this small enzyme makes a new type of homo polymeric complex as required for its activity. The manuscript provides important conceptual novelties that will be of interest for a broad readership of biologists interested in gene expression processes.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Drug Repurposing for the SARS‐CoV‐2 Papain‐Like Protease

1. Chia‐Chuan Cho
2. Shuhua G. Li
3. Tyler J. Lalonde
4. Kai S. Yang
5. Ge Yu
6. Yuchen Qiao
7. Shiqing Xu
8. Wenshe Ray Liu

Reviewed by ScreenIT