PT  - JOURNAL ARTICLE
AU  - Bidyut K Mohanty
AU  - Joseph AQ Karam
AU  - Breege V Howley
AU  - Annamarie C Dalton
AU  - Simon Grelet
AU  - Toros Dincman
AU  - William S Streitfeld
AU  - Je-Hyun Yoon
AU  - Lata Balakrishnan
AU  - Walter J Chazin
AU  - David T Long
AU  - Philip H Howe
TI  - Heterogeneous nuclear ribonucleoprotein E1 binds polycytosine DNA and monitors genome integrity
AID  - 10.26508/lsa.202000995
DP  - 2021 Sep 01
TA  - Life Science Alliance
PG  - e202000995
VI  - 4
IP  - 9
4099  - https://www.life-science-alliance.org/content/4/9/e202000995.short
4100  - https://www.life-science-alliance.org/content/4/9/e202000995.full
SO  - Life Sci. Alliance2021 Sep 01; 4
AB  - Heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) is a tumor suppressor protein that binds site- and structure-specifically to RNA sequences to regulate mRNA stability, facilitate alternative splicing, and suppress protein translation on several metastasis-associated mRNAs. Here, we show that hnRNP E1 binds polycytosine-rich DNA tracts present throughout the genome, including those at promoters of several oncogenes and telomeres and monitors genome integrity. It binds DNA in a site- and structure-specific manner. hnRNP E1-knockdown cells displayed increased DNA damage signals including γ-H2AX at its binding sites and also showed increased mutations. UV and hydroxyurea treatment of hnRNP E1-knockdown cells exacerbated the basal DNA damage signals with increased cell cycle arrest, activation of checkpoint proteins, and monoubiquitination of proliferating cell nuclear antigen despite no changes in deubiquitinating enzymes. DNA damage caused by genotoxin treatment localized to hnRNP E1 binding sites. Our work suggests that hnRNP E1 facilitates functions of DNA integrity proteins at polycytosine tracts and monitors DNA integrity at these sites.