Increased RPA1 gene dosage affects genomic stability potentially contributing to 17p13.3 duplication syndrome.

ABSTRACT: A novel microduplication syndrome involving various-sized contiguous duplications in 17p13.3 has recently been described, suggesting that increased copy number of genes in 17p13.3, particularly PAFAH1B1, is associated with clinical features including facial dysmorphism, developmental delay, and autism spectrum disorder. We have previously shown that patient-derived cell lines from individuals with haploinsufficiency of RPA1, a gene within 17p13.3, exhibit an impaired ATR-dependent DNA damage response (DDR). Here, we show that cell lines from patients with duplications specifically incorporating RPA1 exhibit a different although characteristic spectrum of DDR defects including abnormal S phase distribution, attenuated DNA double strand break (DSB)-induced RAD51 chromatin retention, elevated

SUBMITTER: Outwin E 

PROVIDER: S-EPMC3161930 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature