Publication Date:
2014-11-15
Description:
Replication protein A (RPA) is the main eukaryotic single-stranded DNA (ssDNA) binding protein, having essential roles in all DNA metabolic reactions involving ssDNA. RPA binds ssDNA with high affinity, thereby preventing the formation of secondary structures and protecting ssDNA from the action of nucleases, and directly interacts with other DNA processing proteins. Here, we discuss recent results supporting the idea that one function of RPA is to prevent annealing between short repeats that can lead to chromosome rearrangements by microhomology-mediated end joining or the formation of hairpin structures that are substrates for structure-selective nucleases. We suggest that replication fork catastrophe caused by depletion of RPA could result from cleavage of secondary structures by nucleases, and that failure to cleave hairpin structures formed at DNA ends could lead to gene amplification. These studies highlight the important role RPA plays in maintaining genome integrity. RPA binding to the ssDNA tailed intermediates that are formed during the repair of DNA double-strand breaks prevents annealing between short sequence homologies internal to the ends. When RPA is depleted from cells, or when its DNA binding activity is compromised, annealing between short repeats can lead to mutagenic microhomology-mediated end joining (MMEJ) or hairpin-capped ends.
Print ISSN:
0265-9247
Electronic ISSN:
1521-1878
Topics:
Biology
,
Medicine
