Journal
MOLECULAR CELL
Volume 71, Issue 4, Pages 487-+Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2018.06.037
Keywords
-
Categories
Funding
- NIH [1R35GM118189-01, S10 OD018174]
- Swiss National Science Foundation Fellowships [P300P3_154624, P300PA_167654]
- Swiss National Science Foundation (SNF) [P300P3_154624, P300PA_167654] Funding Source: Swiss National Science Foundation (SNF)
Ask authors/readers for more resources
DNA-RNA hybrids associated with R-loops promote DNA damage and genomic instability. The capacity of hybrids at different genomic sites to cause DNA damage was not known, and the mechanisms leading from hybrid to damage were poorly understood. Here, we adopt a new strategy to map and characterize the sites of hybrid-induced damage genome-wide in budding yeast. We show that hybrid removal is essential for life because persistent hybrids cause irreparable DNA damage and cell death. We identify that a subset of hybrids is prone to cause damage, and the chromosomal context of hybrids dramatically impacts their ability to induce damage. Furthermore, persistent hybrids affect the repair pathway, generating large regions of single-stranded DNA (ssDNA) by two distinct mechanisms, likely resection and re-replication. These damaged regions may act as potential precursors to gross chromosomal rearrangements like deletions and duplications that are associated with R-loops and cancers.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available