Evidence map›Paper›PMID 36536104›Full record

ArticleNature structural & molecular biology2023

Polλ promotes microhomology-mediated end-joining.

Gurushankar Chandramouly, Joonas Jamsen, Nikita Borisonnik, Mrityunjay Tyagi, Marissa L Calbert, Taylor Tredinnick, Ahmet Y Ozdemir, Tatiana Kent, Elena V Demidova, Sanjeevani Arora and 2 more

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.2field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 25 citations in OpenAlex.

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  18. Genomic consequences associated with Agrobacterium-mediated transformation of plants.The Plant journal : for cell and molecular biology · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 2 countries.

Gurushankar Chandramouly *Department of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-4258-9859
Joonas Jamsen *Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.ORCID http://orcid.org/0000-0001-9505-1254
Nikita BorisonnikDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Mrityunjay TyagiDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Marissa L CalbertDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Taylor TredinnickDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Ahmet Y OzdemirSpark Therapeutics, Philadelphia, PA, USA.
Tatiana KentDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Elena V DemidovaCancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
Sanjeevani AroraCancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
Samuel H WilsonGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.ORCID http://orcid.org/0000-0002-1702-5293
Richard T PomerantzDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA. richard.pomerantz@jefferson.edu.ORCID http://orcid.org/0000-0003-1194-9871
Thomas Jefferson University · USFox Chase Cancer Center · USNational Institutes of Health · USSpark Therapeutics (United States) · USUniversity of Arkansas for Medical Sciences · US

Funding

WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Dietmar J Kappes · 1985 to 2026
$138.8M
Structure and Function of DNA Polymerase ThetaR01GM130889 · NIGMS · THOMAS JEFFERSON UNIVERSITY · PI POMERANTZ, RICHARD T · 2019 to 2022
$1.6M
Mechanisms of RNA-DNA repairR01GM137124 · NIGMS · THOMAS JEFFERSON UNIVERSITY · PI POMERANTZ, RICHARD T · 2020 to 2023
$1.5M
Validation of blood-based predictive biomarkers of therapeutic response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal cancerUH2CA271230 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI ARORA, SANJEEVANI, MEYER, JOSHUA E. · 2022 to 2023
$512k
NCI NIH HHS P30 CA006927NCI NIH HHS UH2 CA271230NIGMS NIH HHS R01 GM130889NIGMS NIH HHS R01 GM137124
6 · The paper itself

Abstract

The double-strand break (DSB) repair pathway called microhomology-mediated end-joining (MMEJ) is thought to be dependent on DNA polymerase theta (Polθ) and occur independently of nonhomologous end-joining (NHEJ) factors. An unresolved question is whether MMEJ is facilitated by a single Polθ-mediated end-joining pathway or consists of additional undiscovered pathways. We find that human X-family Polλ, which functions in NHEJ, additionally exhibits robust MMEJ activity like Polθ. Polλ promotes MMEJ in mammalian cells independently of essential NHEJ factors LIG4/XRCC4 and Polθ, which reveals a distinct Polλ-dependent MMEJ mechanism. X-ray crystallography employing in situ photo-induced DSB formation captured Polλ in the act of stabilizing a microhomology-mediated DNA synapse with incoming nucleotide at 2.0 Å resolution and reveals how Polλ performs replication across a DNA synapse joined by minimal base-pairing. Last, we find that Polλ is semisynthetic lethal with BRCA1 and BRCA2. Together, these studies indicate Polλ MMEJ as a distinct DSB repair mechanism.

Indexed as

DNA Breaks, Double-StrandedDNA RepairAnimalsDNADNA End-Joining RepairHumansMammalsDNA

Identifiers

PMID36536104
PMCPMC10197178
OpenAlexW4312199719

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.