Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-020-15954-x
Keywords
-
Categories
Funding
- Wellcome Trust [104158/Z/14/Z]
- Royal Society [104158/Z/14/Z]
- NIH/NIGMS grant [R35GM118052]
- European Research Council [StG-801659]
- Swedish Research Council [2018-03426]
- Cancerfonden [2018/326]
- University of Gothenburg
- Swedish Research Council [2018-03426] Funding Source: Swedish Research Council
- Vinnova [2018-03426] Funding Source: Vinnova
- Wellcome Trust [104158/Z/14/Z] Funding Source: Wellcome Trust
Ask authors/readers for more resources
Breast cancer susceptibility gene II (BRCA2) is central in homologous recombination (HR). In meiosis, BRCA2 binds to MEILB2 to localize to DNA double-strand breaks (DSBs). Here, we identify BRCA2 and MEILB2-associating protein 1 (BRME1), which functions as a stabilizer of MEILB2 by binding to an alpha -helical N-terminus of MEILB2 and preventing MEILB2 self-association. BRCA2 binds to the C-terminus of MEILB2, resulting in the formation of the BRCA2-MEILB2-BRME1 ternary complex. In Brme1 knockout (Brme1(-/-)) mice, the BRCA2-MEILB2 complex is destabilized, leading to defects in DSB repair, homolog synapsis, and crossover formation. Persistent DSBs in Brme1(-/-) reactivate the somatic-like DNA-damage response, which repairs DSBs but cannot complement the crossover formation defects. Further, MEILB2-BRME1 is activated in many human cancers, and somatically expressed MEILB2-BRME1 impairs mitotic HR. Thus, the meiotic BRCA2 complex is central in meiotic HR, and its misregulation is implicated in cancer development. In meiosis, BRCA2 associates to MEILB2 localising at DNA double-strand breaks (DSBs). Here, the authors identify BRCA2 and MEILB2- associating protein 1 termed BRME1 to work together in regulating meiotic recombination.
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