DNA polymerase θ protects leukemia cells from metabolically induced DNA damage.

Leukemia cells accumulate DNA damage, but altered DNA repair mechanisms protect them from apoptosis. We showed here that formaldehyde generated by serine/1-carbon cycle metabolism contributed to the accumulation of toxic DNA-protein crosslinks (DPCs) in leukemia cells, especially in driver clones harboring oncogenic tyrosine kinases (OTKs: FLT3(internal tandem duplication [ITD]), JAK2(V617F), BCR-ABL1). To counteract this effect, OTKs enhanced the expression of DNA polymerase theta (POLθ) via ERK1/2 serine/threonine kinase-dependent inhibition of c-CBL E3 ligase-mediated ubiquitination of POLθ and its proteasomal degradation. Overexpression of POLθ in OTK-positive cells resulted in the efficient repair of DPC-containing DNA double-strand breaks by POLθ-mediated end-joining. The transforming activities of OTKs and other leukemia-inducing oncogenes, especially of those causing the inhibition of BRCA1/2-mediated homologous recombination with and without concomitant inhibition of DNA-PK-dependent nonhomologous end-joining, was abrogated in Polq-/- murine bone marrow cells. Genetic and pharmacological targeting of POLθ polymerase and helicase activities revealed that both activities are promising targets in leukemia cells. Moreover, OTK inhibitors or DPC-inducing drug etoposide enhanced the antileukemia effect of POLθ inhibitor in vitro and in vivo. In conclusion, we demonstrated that POLθ plays an essential role in protecting leukemia cells from metabolically induced toxic DNA lesions triggered by formaldehyde, and it can be targeted to achieve a therapeutic effect.

The ultrastructure of resurrection: Post-diapause development in an Antarctic freshwater copepod.

The copepod, Boeckella poppei, is broadly distributed in Antarctic and subantarctic maritime lakes threatened by climate change and anthropogenic chemicals. Unfortunately, comparatively little is known about freshwater zooplankton in lakes influenced by the Southern Ocean. In order to predict the impact of climate change and chemicals on freshwater species like B. poppei, it is necessary to understand the nature of their most resilient life stages. Embryos of B. poppei survive up to two centuries in a resilient dormant state, but no published studies evaluate the encapsulating wall that protects theses embryos or their development after dormancy. This study fills that knowledge gap by using microscopy to examine development and the encapsulating wall in B. poppei embryos from Antarctica. The encapsulating wall of B. poppei is comprised of three layers that appear to be conserved among crustacean zooplankton, but emergence and hatching are uniquely delayed until the nauplius is fully formed in this species. Diapause embryos in Antarctic sediments appear to be in a partially syncytial mid-gastrula stage. The number of nuclei quadruples between the end of diapause and hatching. Approximately 75% of yolk platelets are completely consumed during the same time period. However, some yolk platelets are left completely intact at the time of hatching. Preservation of complete yolk platelets suggests an all-or-none biochemical process for activating yolk consumption that is inactivated during dormancy to preserve yolk for post-dormancy development. The implications of these and additional ultrastructural features are discussed in the context of anthropogenic influence and the natural environment.

Tyrosine kinase inhibitor-induced defects in DNA repair sensitize FLT3(ITD)-positive leukemia cells to PARP1 inhibitors.

Mutations in FMS-like tyrosine kinase 3 (FLT3), such as internal tandem duplications (ITDs), can be found in up to 23% of patients with acute myeloid leukemia (AML) and confer a poor prognosis. Current treatment options for FLT3(ITD)-positive AMLs include genotoxic therapy and FLT3 inhibitors (FLT3i's), which are rarely curative. PARP1 inhibitors (PARP1i's) have been successfully applied to induce synthetic lethality in tumors harboring BRCA1/2 mutations and displaying homologous recombination (HR) deficiency. We show here that inhibition of FLT3(ITD) activity by the FLT3i AC220 caused downregulation of DNA repair proteins BRCA1, BRCA2, PALB2, RAD51, and LIG4, resulting in inhibition of 2 major DNA double-strand break (DSB) repair pathways, HR, and nonhomologous end-joining. PARP1i, olaparib, and BMN673 caused accumulation of lethal DSBs and cell death in AC220-treated FLT3(ITD)-positive leukemia cells, thus mimicking synthetic lethality. Moreover, the combination of FLT3i and PARP1i eliminated FLT3(ITD)-positive quiescent and proliferating leukemia stem cells, as well as leukemic progenitors, from human and mouse leukemia samples. Notably, the combination of AC220 and BMN673 significantly delayed disease onset and effectively reduced leukemia-initiating cells in an FLT3(ITD)-positive primary AML xenograft mouse model. In conclusion, we postulate that FLT3i-induced deficiencies in DSB repair pathways sensitize FLT3(ITD)-positive AML cells to synthetic lethality triggered by PARP1i's. Therefore, FLT3(ITD) could be used as a precision medicine marker for identifying AML patients that may benefit from a therapeutic regimen combining FLT3 and PARP1i's.

Effects of an Upper-Body Training Program Involving Resistance Exercise and High-Intensity Arm Cranking on Peak Handcycling Performance and Wheelchair Propulsion Efficiency in Able-Bodied Men.

Chaikhot, D, Reed, K, Petroongrad, W, Athanasiou, F, van Kooten, D, and Hettinga, FJ. Effects of an upper-body training program involving resistance exercise and high-intensity arm cranking on peak handcycling performance and wheelchair propulsion efficiency in able-bodied men. J Strength Cond Res 34(8): 2267-2275, 2020-The aim of this study was to determine the training effects of an upper-body training program involving resistance exercise and high-intensity arm cranking on peak handcycling performance, propulsion efficiency, and biomechanical characteristics of wheelchair propulsion in able-bodied men. The training group (n = 10) received a 4-week upper-body resistance training (RT), 70% of 1 repetition maximum, 3 sets of 10 repetitions, 8 exercise stations, 2 times per week, combined with high-intensity interval training (HIIT) 2 times per week. High-intensity interval training consisted of arm-crank exercise, 7 intervals of 2 minutes at 80-90% of peak heart rate (HRpeak) with 2-minute active rest at 50-60% of HRpeak. The control group (n = 10) received no training. Both groups performed a preincremental and postincremental handcycling test until volitional exhaustion to evaluate fitness and a 4-minute submaximal wheelchair propulsion test at comfortable speed (CS), 125 and 145% of CS, to evaluate gross mechanical efficiency (GE), fraction of effective force (FEF), percentage of peak oxygen consumption (% V[Combining Dot Above]O2peak), and propulsion characteristics. Repeated-measures analysis of variance was performed (p < 0.05). Training resulted in a 28.2 ± 16.5% increase in peak power output, 13.3 ± 7.5% increase in V[Combining Dot Above]O2peak, 5.6 ± 0.9% increase in HRpeak, and 3.8 ± 1.5% decrease in HRrest. No training effects on FEF, GE, % V[Combining Dot Above]O2peak, and push characteristics were identified. In conclusion, the combined RT and arm-cranking HIIT improved fitness. However, it seems that this training did not result in improvements in propulsion efficiency and push characteristics. Additional wheelchair skill training may be needed to fully benefit from this advantage in daily life propulsion.

Novel allosteric PARP1 inhibitors for the treatment of BRCA-deficient leukemia.

The successful use of PARP1 inhibitors like olaparib (Loparza®) in the treatment of BRCA1/2- deficient breast cancer has provided clinical proof of concept for applying personalized medicine based on synthetic lethality to the treatment of cancer. Unfortunately, all marketed PARP1 inhibitors act by competing with the cofactor NAD+ and resistance is already developing to this anti-cancer mechanism. Allosteric PARP1 inhibitors could provide a means of overcoming this resistance. A high throughput screen performed by Tulin et al. identified 5F02 as an allosteric PARP inhibitor that acts by preventing the enzymatic activation of PARP1 by histone H4. 5F02 demonstrated anti-cancer activity in several cancer cell lines and was more potent than olaparib and synergistic with olaparib in these assays. In the present study we explored the structure-activity relationship of 5F02 by preparing analogs that possessed structural variation in four regions of the chemical scaffold. Our efforts led to lead molecule 7, which demonstrated potent anti-clonogenic activity against BRCA-deficient NALM6 leukemia cells in culture and a therapeutic index for the BRCA-deficient cells over their BRCA-proficient isogenic counterparts.

Disaster journalism: fostering citizen and community disaster mitigation, preparedness, response, recovery, and resilience across the disaster cycle.

Natural and human-caused disasters pose a significant risk to the health and well-being of people. Journalists and news organisations can fulfil multiple roles related to disasters, ranging from providing warnings, assessing disaster mitigation and preparedness, and reporting on what occurs, to aiding long-term recovery and fostering disaster resilience. This paper considers these possible functions of disaster journalism and draws on semi-structured interviews with 24 journalists in the United States to understand better their approach to the discipline. A thematic analysis was employed, which resulted in the identification of five main themes and accompanying subthemes: (i) examining disaster mitigation and preparedness; (ii) facilitating recovery; (iii) self-care and care of journalists; (iv) continued spread of social media; and (v) disaster journalism ethics. The paper concludes that disaster journalism done poorly can result in harm, but done well, it can be an essential instrument with respect to public disaster planning, management, response, and recovery.

Oxidative coupling of Michael acceptors with aryl nucleophiles produced through rhodium-catalyzed C-C bond activation.

Utilizing rhodium catalysis, aryl nucleophiles generated via carbon-carbon single bond activation successfully undergo oxidative coupling with Michael acceptors. The reaction scope encompasses a broad range of nucleophiles generated from quinolinyl ketones as well as a series of electron deficient terminal alkenes, illustrating the broad potential of intersecting carbon-carbon bond activation with synthetically useful coupling methodologies. The demonstrated oxidative coupling produces a range of cinnamyl derivatives, several of which are challenging to prepare via conventional routes.

Every second counts: innovations to increase timely defibrillation rates.

Early defibrillation is an essential step in the "chain of survival" for patients with in-hospital cardiac arrest. To increase the rate of early defibrillation by nurse first responders in noncritical care areas, our institution employed a quality resuscitation consultant, implemented nursing education programs, and standardized equipment and practices. Automated external defibrillator application by nurse first responders prior to advanced cardiac life support team arrival has improved from 15% in 2011 to 76% in 2013 (P < .001).

Reversible intracellular acidification and depletion of NTPs provide a potential physiological origin for centuries of dormancy in an Antarctic freshwater copepod.

A great diversity of crustacean zooplankton found in inland and coastal waters produce embryos that settle into bottom sediments to form an egg bank. Embryos from these banks can remain dormant for centuries, creating a reservoir of genetic diversity. A large body of literature describes the ecological and evolutionary importance of zooplankton egg banks. However, literature on the physiological traits behind dormancy in crustacean zooplankton are limited. Most data on the physiology of dormancy comes from research on one species of anostracan, the brine shrimp, Artemia franciscana. Anoxia-induced dormancy in this species is facilitated by a profound and reversible acidification of the intracellular space. This acidification is accompanied by a reversible depletion of adenosine triphosphate (ATP). The present study demonstrates that acidification of the intracellular space also occurs in concert with a depletion of nucleoside triphosphates (NTPs) in the Antarctic copepod, Boeckella poppei. Like A. franciscana, the depletion of NTPs and acidification are rapidly reversed during aerobic recovery in B. poppei. These data provide the first comparative evidence that extreme dormancy under anoxia in crustacean zooplankton is associated with intracellular acidification and an ability to recover from the depletion of ATP.

Creative Arts Therapy for Healthcare Professionals Is Associated With Long-Term Improvements in Psychological Distress.

OBJECTIVE: Burnout in healthcare professionals (HCPs) is a pressing issue in healthcare. We report the long-term impact of our previous creative arts therapy (CAT) intervention for reducing psychological distress in HCPs. METHODS: Healthcare professionals were randomized to CAT intervention or control group. The CAT group completed surveys evaluating symptoms of psychological distress at 4 months, 8 months, and 1 year postintervention, whereas the control group completed surveys at the 1-year mark. RESULTS: The CAT group demonstrated sustained improvement in distress scores for anxiety, depression, and affect at 4 and 8 months postintervention. At the 12-month mark, the CAT group exhibited improvements in anxiety, depression, and affect compared with the control group. CONCLUSION: Creative arts therapy has lasting benefits for HCPs. Long-term follow-ups are crucial for assessing sustainability, and further investigation should focus on disseminating and implementing CAT programs for HCPs.

Haploinsufficiency of ZNF251 causes DNA-PKcs-dependent resistance to PARP inhibitors in BRCA1-mutated cancer cells.

Poly (ADP-ribose) polymerase (PARP) inhibitors represent a promising new class of agents that have demonstrated efficacy in treating various cancers, particularly those that carry BRCA1/2 mutations. The cancer associated BRCA1/2 mutations disrupt DNA double strand break (DSB) repair by homologous recombination (HR). PARP inhibitors (PARPis) have been applied to trigger synthetic lethality in BRCA1/2-mutated cancer cells by promoting the accumulation of toxic DSBs. Unfortunately, resistance to PARPis is common and can occur through multiple mechanisms, including the restoration of HR and/or the stabilization of replication forks. To gain a better understanding of the mechanisms underlying PARPi resistance, we conducted an unbiased CRISPR-pooled genome-wide library screen to identify new genes whose deficiency confers resistance to the PARPi olaparib. Our study revealed that ZNF251, a transcription factor, is a novel gene whose haploinsufficiency confers PARPi resistance in multiple breast and ovarian cancer lines harboring BRCA1 mutations. Mechanistically, we discovered that ZNF251 haploinsufficiency leads to constitutive stimulation of DNA-PKcs-dependent non-homologous end joining (NHEJ) repair of DSBs and DNA-PKcs-mediated fork protection in BRCA1-mutated cancer cells (BRCA1mut + ZNF251KD). Moreover, we demonstrated that DNA-PKcs inhibitors can restore PARPi sensitivity in BRCA1mut + ZNF251KD cells ex vivo and in vivo. Our findings provide important insights into the mechanisms underlying PARPi resistance and highlight the unexpected role of DNA-PKcs in this phenomenon.

Evaluation of computer-based training and high-fidelity simulation to improve early recognition of sepsis on the adult general ward.

This quality improvement project involved developing, implementing and evaluating an educational intervention using computer-based training (CBT) and high-fidelity simulation (HFS) to increase knowledge, confidence and compliance of nurses identifying sepsis. A one-group pretest-posttest design was used. Participants were nurses on a general ward of an academic medical centre. Study variables were measured over three timepoints: 2 weeks before, immediately after and 90 days after implementation. Data were collected from January 30, 2018, to June 22, 2018. SQUIRE 2.0 checklist for quality improvement reporting used. Improvements in knowledge of sepsis (F(2,83)  = 18.14, p < 0.001, ηp 2  = 0.30) and confidence in early recognition of sepsis (F(2,83)  = 13.67, p < 0.001, ηp 2  = 0.25) were found. Additionally, compliance with sepsis screening improved between the preimplementation and postimplementation period (χ2  = 13.633, df = 1, p < 0.001). Overall, the nurses evaluated their experience with the CBT and HFS as strongly positive. When designing and implementing an educational intervention on sepsis, a process for follow-up which provides reinforcement should be considered to retain nurses' knowledge.

Simultaneous Targeting of DNA Polymerase Theta and PARP1 or RAD52 Triggers Dual Synthetic Lethality in Homologous Recombination-Deficient Leukemia Cells.

DNA polymerase theta (Polθ, encoded by POLQ gene) plays an essential role in Polθ-mediated end-joining (TMEJ) of DNA double-strand breaks (DSB). Inhibition of Polθ is synthetic lethal in homologous recombination (HR)-deficient tumor cells. However, DSBs can be also repaired by PARP1 and RAD52-mediated mechanisms. Because leukemia cells accumulate spontaneous DSBs, we tested if simultaneous targeting of Polθ and PARP1 or RAD52 enhance the synthetic lethal effect in HR-deficient leukemia cells. Transformation potential of the oncogenes inducing BRCA1/2-deficiency (BCR-ABL1 and AML1-ETO) was severely limited in Polq-/-;Parp1-/- and Polq-/-;Rad52-/- cells when compared with single knockouts, which was associated with accumulation of DSBs. Small-molecule inhibitor of Polθ (Polθi) when combined with PARP or RAD52 inhibitors (PARPi, RAD52i) caused accumulation of DSBs and exerted increased effect against HR-deficient leukemia and myeloproliferative neoplasm cells. IMPLICATIONS: In conclusion, we show that PARPi or RAD52i might improve therapeutic effect of Polθi against HR-deficient leukemias.

The Effect of Creative Arts Therapy on Psychological Distress in Health Care Professionals.

BACKGROUND: Work-related psychological distress is common among health care professionals. We determined whether 4 creative arts therapy (CAT) programs were acceptable, feasible, and improved psychological distress and job turnover intention in health care professionals with burnout symptoms. METHODS: Health care professionals were enrolled during the coronavirus disease (COVID-19) pandemic from September 2020 until July 2021. Participants attended in-person weekly 90-minute group session for 12 consecutive weeks. Intervention and control subjects completed surveys before the beginning and after the end of their cohort. The study outcomes were session attendance (feasibility), program satisfaction (acceptability), and change in symptoms of anxiety, depression, burnout, posttraumatic stress disorder (PTSD), and job turnover intention. RESULTS: We randomized 165 participants into 4 CAT interventions and 1 common control group across 3 sequential cohorts. Thirty-five randomized participants dropped out before the start of the cohort, and 16 were replaced from a waiting list. Therefore, the cohort consisted of 146 participants. On average, participants were 35 years old, white (85%), and female (92%). Overall, 52% were nurses, 10% were doctors, and 16% were behavioral health specialists. Participants attended a median of 9.5 [8-11] sessions. Program satisfaction was high with a median Client Satisfaction Questionnaire (CSQ-8) score of 31 [17-32] out of a possible score of 32. Participants randomized to the intervention had improvements in anxiety (P < .0001) and depression scores (P = .0007), total posttraumatic stress disorder score (P =.0002), burnout scores (P = .001, .003, .008), and turnover intention (P = .001). CONCLUSIONS: A CAT program is feasible, acceptable, and may reduce psychological distress and turnover intention for health care professionals.

Neighborhood Characteristics, Parental Practices and Children's Math Achievement in Elementary School.

This paper investigates the relationships among neighborhood characteristics, education-related parental practices, and children's academic achievement during a critical but under-studied stage of children's educational trajectories - the elementary school years. Using a large, nationally representative database of American elementary school students - the Early Childhood Longitudinal Study - Kindergarten Cohort (ECLS-K) - and contextual data from the 2000 U.S. Census, we examine parental practices and neighborhood characteristics at the beginning of children's school careers (grades K-1) and their associations with math achievement through the end of the 5th grade. FINDINGS: Net of family-level characteristics, higher levels of early education- oriented parental practices were associated with higher mathematics achievement at the end of 5th grade, while neighborhood disadvantage was associated with lower 5th grade math achievement. Families residing in high poverty, high unemployment, low-education neighborhoods employed fewer education- oriented practices with their kindergarten- first grade children, but the positive effect of such parental practices on children's mathematics achievement was stronger for children who live in disadvantaged neighborhoods.

Polθ promotes the repair of 5'-DNA-protein crosslinks by microhomology-mediated end-joining.

DNA polymerase θ (Polθ) confers resistance to chemotherapy agents that cause DNA-protein crosslinks (DPCs) at double-strand breaks (DSBs), such as topoisomerase inhibitors. This suggests Polθ might facilitate DPC repair by microhomology-mediated end-joining (MMEJ). Here, we investigate Polθ repair of DSBs carrying DPCs by monitoring MMEJ in Xenopus egg extracts. MMEJ in extracts is dependent on Polθ, exhibits the MMEJ repair signature, and efficiently repairs 5' terminal DPCs independently of non-homologous end-joining and the replisome. We demonstrate that Polθ promotes the repair of 5' terminal DPCs in mammalian cells by using an MMEJ reporter and find that Polθ confers resistance to formaldehyde in addition to topoisomerase inhibitors. Dual deficiency in Polθ and tyrosyl-DNA phosphodiesterase 2 (TDP2) causes severe cellular sensitivity to etoposide, which demonstrates MMEJ as an independent DPC repair pathway. These studies recapitulate MMEJ in vitro and elucidate how Polθ confers resistance to etoposide.

TET2 and DNMT3A Mutations Exert Divergent Effects on DNA Repair and Sensitivity of Leukemia Cells to PARP Inhibitors.

Somatic variants in TET2 and DNMT3A are founding mutations in hematological malignancies that affect the epigenetic regulation of DNA methylation. Mutations in both genes often co-occur with activating mutations in genes encoding oncogenic tyrosine kinases such as FLT3ITD, BCR-ABL1, JAK2V617F , and MPLW515L , or with mutations affecting related signaling pathways such as NRASG12D and CALRdel52 . Here, we show that TET2 and DNMT3A mutations exert divergent roles in regulating DNA repair activities in leukemia cells expressing these oncogenes. Malignant TET2-deficient cells displayed downregulation of BRCA1 and LIG4, resulting in reduced activity of BRCA1/2-mediated homologous recombination (HR) and DNA-PK-mediated non-homologous end-joining (D-NHEJ), respectively. TET2-deficient cells relied on PARP1-mediated alternative NHEJ (Alt-NHEJ) for protection from the toxic effects of spontaneous and drug-induced DNA double-strand breaks. Conversely, DNMT3A-deficient cells favored HR/D-NHEJ owing to downregulation of PARP1 and reduction of Alt-NHEJ. Consequently, malignant TET2-deficient cells were sensitive to PARP inhibitor (PARPi) treatment in vitro and in vivo, whereas DNMT3A-deficient cells were resistant. Disruption of TET2 dioxygenase activity or TET2-Wilms' tumor 1 (WT1)-binding ability was responsible for DNA repair defects and sensitivity to PARPi associated with TET2 deficiency. Moreover, mutation or deletion of WT1 mimicked the effect of TET2 mutation on DSB repair activity and sensitivity to PARPi. Collectively, these findings reveal that TET2 and WT1 mutations may serve as biomarkers of synthetic lethality triggered by PARPi, which should be explored therapeutically. SIGNIFICANCE: TET2 and DNMT3A mutations affect distinct DNA repair mechanisms and govern the differential sensitivities of oncogenic tyrosine kinase-positive malignant hematopoietic cells to PARP inhibitors.

Iron deficiency in female pattern hair loss, chronic telogen effluvium, and control groups.

BACKGROUND: The literature suggests that iron deficiency (ID) may play a role in female pattern hair loss (FPHL) or in chronic telogen effluvium (CTE). OBJECTIVE: We sought to determine if ID is more common in women with FPHL and/or CTE than in control subjects without hair loss. METHODS: This was a controlled study of 381 Caucasian women aged 18 years or older with FPHL or CTE seen in the Duke University Hair Disorders Clinic, Durham, NC, and 76 Caucasian women aged 18 years or older from the university environs who had no history or physical findings of hair loss (control subjects). All participants had to have at least a serum ferritin and hemoglobin reading and history of menopausal status. RESULTS: When ferritin less than or equal to 15 µg/L was used as the definition, ID occurred in 12.4%, 12.1%, and 29.8% of premenopausal women with FPHL (n = 170), CTE (n = 58), and control subjects (n = 47), respectively, and in 1.7%, 10.5%, and 6.9% of postmenopausal women with FPHL (n = 115), CTE (n = 38), and control subjects (n = 29), respectively. When ferritin less than or equal to 40 µg/L was used as the definition, ID occurred in 58.8%, 63.8%, and 72.3% of premenopausal women with FPHL, CTE, and control subjects, respectively, and in 26.1%, 36.8%, and 20.7% of postmenopausal women with FPHL, CTE, and control subjects, respectively. There was no statistically significant increase in the incidence of ID in premenopausal or postmenopausal women with FPHL or CTE versus control subjects. LIMITATIONS: The effect of correction of ID on hair loss is unknown. CONCLUSION: ID is common in women but not increased in patients with FPHL or CTE compared with control subjects.

Creative Arts Therapy as a Potential Intervention to Prevent Burnout and Build Resilience in Health Care Professionals.

The delivery of health care is undergoing a rapid evolution that is dramatically changing the way health care professionals perform their job responsibilities. In this increasingly stressful work environment, professionals are experiencing alarming rates of burnout. Recent efforts to enhance wellness have been directed toward organizations. However, because of the nature of the work performed in intensive care units, interventions to develop individual resilience are also needed. Currently, medical centers are environments in which the emotional impact of work-related trauma is often minimized and rarely processed. Some individuals may struggle to describe or express the impact of those traumas. Through nonverbal interventions, creative arts therapy can help people access, explore, and share authentic emotion in visual, musical, physical, or written form. By reconstructing meaning through transformative methods, participants may confront, reflect, and better cope with traumatic experiences while catalyzing social support networks and deepening relational bonds in the workplace.

Publisher Correction: Molecular basis of microhomology-mediated end-joining by purified full-length Polθ.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.