Abstract:
:R loop, a transcription intermediate containing RNA:DNA hybrids and displaced single-stranded DNA (ssDNA), has emerged as a major source of genomic instability. RNaseH1, which cleaves the RNA in RNA:DNA hybrids, plays an important role in R loop suppression. Here we show that replication protein A (RPA), an ssDNA-binding protein, interacts with RNaseH1 and colocalizes with both RNaseH1 and R loops in cells. In vitro, purified RPA directly enhances the association of RNaseH1 with RNA:DNA hybrids and stimulates the activity of RNaseH1 on R loops. An RPA binding-defective RNaseH1 mutant is not efficiently stimulated by RPA in vitro, fails to accumulate at R loops in cells, and loses the ability to suppress R loops and associated genomic instability. Thus, in addition to sensing DNA damage and replication stress, RPA is a sensor of R loops and a regulator of RNaseH1, extending the versatile role of RPA in suppression of genomic instability.
journal_name
Mol Celljournal_title
Molecular cellauthors
Nguyen HD,Yadav T,Giri S,Saez B,Graubert TA,Zou Ldoi
10.1016/j.molcel.2017.01.029subject
Has Abstractpub_date
2017-03-02 00:00:00pages
832-847.e4issue
5eissn
1097-2765issn
1097-4164pii
S1097-2765(17)30055-2journal_volume
65pub_type
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