Dataset Information
LAP2α preserves genome integrity through assisting RPA deposition on damaged chromatin.
Ontology highlight
ABSTRACT: Background
Single-stranded DNA (ssDNA) coated with replication protein A (RPA) acts as a key platform for the recruitment and exchange of genome maintenance factors in DNA damage response. Yet, how the formation of the ssDNA-RPA intermediate is regulated remains elusive.Results
Here, we report that the lamin-associated protein LAP2α is physically associated with RPA, and LAP2α preferentially facilitates RPA deposition on damaged chromatin via physical contacts between LAP2α and RPA1. Importantly, LAP2α-promoted RPA binding to ssDNA plays a critical role in protection of replication forks, activation of ATR, and repair of damaged DNA. We further demonstrate that the preference of LAP2α-promoted RPA loading on damaged chromatin depends on poly ADP-ribose polymerase PARP1, but not poly(ADP-ribosyl)ation.Conclusions
Our study provides mechanistic insight into RPA deposition in response to DNA damage and reveals a genome protection role of LAP2α.
SUBMITTER: Bao K
PROVIDER: S-EPMC8883701 | biostudies-literature | 2022 Feb
REPOSITORIES: biostudies-literature
Publications
LAP2α preserves genome integrity through assisting RPA deposition on damaged chromatin.
Genome biology 20220228 1
<h4>Background</h4>Single-stranded DNA (ssDNA) coated with replication protein A (RPA) acts as a key platform for the recruitment and exchange of genome maintenance factors in DNA damage response. Yet, how the formation of the ssDNA-RPA intermediate is regulated remains elusive.<h4>Results</h4>Here, we report that the lamin-associated protein LAP2α is physically associated with RPA, and LAP2α preferentially facilitates RPA deposition on damaged chromatin via physical contacts between LAP2α and R ...[more]