<i>RPS19</i> and <i>RPL5</i>, the most commonly mutated genes in Diamond Blackfan anemia, impact DNA double-strand break repair.

ABSTRACT: Diamond Blackfan anemia (DBA) is caused by germline heterozygous loss-of-function pathogenic variants (PVs) in ribosomal protein (RP) genes, most commonly RPS19 and RPL5. In addition to red cell aplasia, individuals with DBA are at increased risk of various cancers. Importantly, the mechanism(s) underlying cancer predisposition are poorly understood. We found that DBA patient-derived lymphoblastoid cells had persistent γ-H2AX foci following ionizing radiation (IR) treatment, suggesting DNA double-strand break (DSB) repair defects. RPS19- and RPL5-knocked down (KD) CD34+ cells had delayed repair of IR-induced DSBs, further implicating these RPs in DSB repair. Assessing the impact of RPS19- and RPL5-KD on specific DSB repair pathways, we found RPS19-KD decreased the efficiency

SUBMITTER: DeCleene NF 

PROVIDER: S-EPMC11482920 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature