R-loops cause genomic instability in T helper lymphocytes from patients with Wiskott-Aldrich syndrome.

ABSTRACT:

Background

Wiskott-Aldrich syndrome (WAS), X-linked thrombocytopenia (XLT), and X-linked neutropenia, which are caused by WAS mutations affecting Wiskott-Aldrich syndrome protein (WASp) expression or activity, manifest in immunodeficiency, autoimmunity, genomic instability, and lymphoid and other cancers. WASp supports filamentous actin formation in the cytoplasm and gene transcription in the nucleus. Although the genetic basis for XLT/WAS has been clarified, the relationships between mutant forms of WASp and the diverse features of these disorders remain ill-defined.

Objective

We sought to define how dysfunctional gene transcription is causally linked to the degree of T_H cell deficiency and genomic instability in the XLT/WAS clinical spectrum.

Methods

In h

SUBMITTER: Sarkar K 

PROVIDER: S-EPMC6003829 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature