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. 2023 Jul 29:2023:10.17912/micropub.biology.000934.
doi: 10.17912/micropub.biology.000934. eCollection 2023.

53bp1 mutation enhances brca1 and bard1 embryonic lethality in C. elegans

Affiliations

53bp1 mutation enhances brca1 and bard1 embryonic lethality in C. elegans

Sara Hariri et al. MicroPubl Biol. .

Abstract

In mice, mutation of brca1 results in embryonic lethality, which is partially suppressed by 53bp1 mutation. In contrast, mutation of the C. elegans BRCA1 ortholog, brc-1 , or its binding partner, brd-1 , lead to only mild embryonic lethality. We show that in C. elegans , brc-1 and brd-1 embryonic lethality is enhanced when 53bp1 ortholog, hsr-9 , is also mutated. This is not a consequence of activating polq-1 -dependent microhomology-mediated end joining, as polq-1 mutation does not suppress embryonic lethality of hsr-9 ; brc-1 mutants. Together, these results suggest that BRC-1 - BRD-1 and HSR-9 function in parallel pathways and do not act antagonistically as in mammals.

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Conflict of interest statement

The authors declare that there are no conflicts of interest present.

Figures

Figure 1.
<b>
Embryonic lethality in different allele combinations of
<i>brc-1, brd-1, hsr-9, </i>
and
<i>polq-1</i>
</b>
Figure 1. Embryonic lethality in different allele combinations of brc-1, brd-1, hsr-9, and polq-1
A) Embryonic lethality in wild type (26), brc-1(xoe4) (12), hsr-9(xoe17); brc-1(xoe4) (25), hsr-9(xoe17) (23) , hsr-9(ok759); brc-1(xoe4) (12) , hsr-9(ok759) (12) , hsr-9(xoe17); brc-1(tm1145) (11) , brc-1(tm1145) (11) , hsr-9(xoe17); brd-1(xoe18) (10), and brd-1(xoe18) (12) animals. Number of animals examined are in paratheses. B) Embryonic lethality in hsr-9(xoe17); brc-1(xoe4) (25), hsr-9(xoe17); brc-1(xoe4) polq-1(xoe51) (20) , brc-1(xoe4) polq-1(xoe51) (18) , hsr-9(xoe17); polq-1(xoe45) (10) and polq-1(xoe51) (12). Mean and 95% Confidence Interval shown; *** p < 0.001; ** p < 0.01; ns = not significant by Mann-Whitney.

References

    1. Boulton SJ, Martin JS, Polanowska J, Hill DE, Gartner A, Vidal M. BRCA1/BARD1 orthologs required for DNA repair in Caenorhabditis elegans. Curr Biol. 2004 Jan 6;14(1):33–39. doi: 10.1016/j.cub.2003.11.029. - DOI - PubMed
    1. Brzovic PS, Keeffe JR, Nishikawa H, Miyamoto K, Fox D 3rd, Fukuda M, Ohta T, Klevit R. Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex. Proc Natl Acad Sci U S A. 2003 May 5;100(10):5646–5651. doi: 10.1073/pnas.0836054100. - DOI - PMC - PubMed
    1. Cao L, Xu X, Bunting SF, Liu J, Wang RH, Cao LL, Wu JJ, Peng TN, Chen J, Nussenzweig A, Deng CX, Finkel T. A selective requirement for 53BP1 in the biological response to genomic instability induced by Brca1 deficiency. Mol Cell. 2009 Aug 28;35(4):534–541. doi: 10.1016/j.molcel.2009.06.037. - DOI - PMC - PubMed
    1. Chen J, Li P, Song L, Bai L, Huen MSY, Liu Y, Lu LY. 53BP1 loss rescues embryonic lethality but not genomic instability of BRCA1 total knockout mice. Cell Death Differ. 2020 Mar 5;27(9):2552–2567. doi: 10.1038/s41418-020-0521-4. - DOI - PMC - PubMed
    1. Hashizume R, Fukuda M, Maeda I, Nishikawa H, Oyake D, Yabuki Y, Ogata H, Ohta T. The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation. J Biol Chem. 2001 Mar 6;276(18):14537–14540. doi: 10.1074/jbc.C000881200. - DOI - PubMed

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