The plant‐specific CDKB 1‐ CYCB 1 complex mediates homologous recombination repair in Arabidopsis

Abstract

Upon DNA damage, cyclin‐dependent kinases (CDKs) are typically inhibited to block cell division. In many organisms, however, it has been found that CDK activity is required for DNA repair, especially for homology‐dependent repair (HR), resulting in the conundrum how mitotic arrest and repair can be reconciled. Here, we show that Arabidopsis thaliana solves this dilemma by a division of labor strategy. We identify the plant‐specific B1‐type CDKs (CDKB1s) and the class of B1‐type cyclins (CYCB1s) as major regulators of HR in plants. We find that RADIATION SENSITIVE 51 (RAD51), a core mediator of HR, is a substrate of CDKB1‐CYCB1 complexes. Conversely, mutants in CDKB1 and CYCB1 fail to recruit RAD51 to damaged DNA. CYCB1;1 is specifically activated after DNA damage and we show that this activation is directly controlled by SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1), a transcription factor that acts similarly to p53 in animals. Thus, while the major mitotic cell‐cycle activity is blocked after DNA damage, CDKB1‐CYCB1 complexes are specifically activated to mediate HR.

Interregulation of CDKA/CDK1 and the Plant-Specific Cyclin-Dependent Kinase CDKB in Control of the Chlamydomonas Cell Cycle

“…Degradation of cyclin B is also critical in plants, since cyclin B with a mutated destruction box inhibits late mitotic events (Weingartner et al 2004). In Arabidopsis, the CYCB1 family (comprising four of the twelve Arabidopsis B-type cyclins) is thought to be involved in DNA repair, possibly in conjunction with members of the CDKB1 family (Weimer et al 2016), in addition to having a role in regulating mitosis (Schnittger et al 2002).…”

SUPPRESSOR OF GAMMA RESPONSE1 Links DNA Damage Response to Organ Regeneration

“…Nonetheless, it is likely that various SOG1-induced genes contribute to root growth recovery after DNA damage, which can be appreciated by the hypersensitivity of relevant mutants to DNA damage. For example, the growth of cycb1;1 and rad51 mutants is compromised in response to cisplatin, a DNA cross linker and DSB-inducer (Weimer et al, 2016a). Similarly, brca1 mutants show enhanced cell death to Mitomycin C, a DNA cross linker (Horvath et al, 2017).…”

“…CDKB1;2, CDKB2;1, and KNOLLE [Yoshiyama et al, 2009;Missirian et al, 2014]), while directly up-regulating other factors (e.g. CYCB1;1, SMR-5,7 [Weimer et al, 2016a;Yi et al, 2014], and WEE1 indirectly [De Schutter et al, 2007, Cools et al, 2011). IR-induced SOG1 also transcriptionally activates DNA repair genes, including BRCA1 and RAD51 (Yoshiyama et al, 2009), which function in homologous recombination (HR)-based repair in S and G2 phase during normal growth (Shrivastav et al, 2008;Menges et al, 2003).…”

“…IR-induced SOG1 also transcriptionally activates DNA repair genes, including BRCA1 and RAD51 (Yoshiyama et al, 2009), which function in homologous recombination (HR)-based repair in S and G2 phase during normal growth (Shrivastav et al, 2008;Menges et al, 2003). SOG1 appears to mediate (via upregulated CYCB1;1, in complex with CDKB1) damage-localized HR repair by BRCA1 and RAD51, in conjunction with RBR1 (Biedermann et al, 2017;Weimer et al, 2016a;Horvath et al, 2017). HR repair can help to restore a damaged cell's genomic integrity in addition to the faster (Mao et al, 2008), predominating canonical nonhomologous end-joining repair pathway (Čermák et al, 2017).…”

Specialization of CDK regulation under DNA damage

“…In Weimer et al, 2 we conclude that, while the major mitotic force, including mitosis-specific CDKs, is inactivated upon DNA damage in a SOG1-dependent manner, SOG1 directly induces CYCB1 expression and activates CDKB1-CYCB1 complexes, which can then mediate HR (Fig. 1).…”