FAN1 removes triplet repeat extrusions via a PCNA- and RFC-dependent mechanism.

Human genome-wide association studies have identified and several DNA mismatch repair (MMR) genes as modifiers of Huntington's disease age of onset. In animal models, FAN1 prevents somatic expansion of CAG triplet repeats, whereas MMR proteins promote this process. To understand the molecular basis of these opposing effects, we evaluated FAN1 nuclease function on DNA extrahelical extrusions that represent key intermediates in triplet repeat expansion.

Comparative Outcomes of Second-line Topoisomerase-I Inhibitor Therapies on Neuroendocrine Carcinoma.

Introduction: This investigation aims to assess the outcomes for second-line therapies to treat extrapulmonary neuroendocrine carcinoma (EP-NEC) after first-line platinum-based chemotherapy.

Methods: With IRB approval, we conducted a retrospective study of EP-NEC patients that progressed on first-line platinum chemotherapy from 2008 to 2018. Demographic data and treatment-related characteristics were collected and represented as descriptive statistics.