Biology subjects

Kolarova, K.

Publications and source records attributed to Kolarova, K..

3 recordsLinked to original sources

bioRxiv2024

CRL4DCAF12 regulation of MCMBP ensures optimal licensing of DNA replication

The minichromosome maintenance (MCM2-7) protein complexes are central drivers of genome duplication. Distinct protein pools, parental and nascent MCMs, and their precise equilibrium are essential to sustain error-free DNA replication1. However, the mechanism responsible for generating these pools and maintaining their equilibrium remains largely unexplored. Here, we identified CRL4DCAF12 as a new factor controlling the assembly of nascent MCM complexes. During MCM biogenesis, MCMBP facilitates the assembly and transport of newly synthesized MCM3-7 subcomplexes into the nucleus2,3. Once in the nucleus, the MCM2 subunit must be incorporated into the MCM3-7 subcomplex, while MCMBP needs to be removed. CRL4DCAF12 facilitates the degradation of MCMBP and thereby regulates the assembly of MCM2-7 complexes. The absence of CRL4DCAF12 adversely affects the level of chromatin-bound nascent MCMs, resulting in accelerated replication forks and genome instability. Collectively, our findings uncovered the molecular mechanism underlying nascent MCM production essential to counteract genome instability and tumor formation.

cell biology↗

bioRxiv2023

Matters Arising: FBXO38 does not control PD-1 stability

SKP1-CUL1-F-box protein (SCF) ubiquitin ligases are versatile protein complexes that mediate the ubiquitination of substrates, which are recognized by their F-box-domain- containing subunits1. One of these substrate receptors is FBXO38. Its gene has been found to be mutated in several families with early-onset distal hereditary motor neuronopathy2. SCFFBXO38 ubiquitin ligase controls the stability of ZXDB, a nuclear factor associated with the centromeric chromatin protein CENP-B3. Moreover, the loss of FBXO38 results in growth retardation and defect in spermatogenesis characterized by deregulation of the Sertoli cell transcription program and centromere integrity4. A report by Meng et al. proposed that SCFFBXO38 regulates the protein levels of the PD-1 inhibitory receptor (also known as CD279, PDCD1) in T cells5. Here, we have re-addressed the conclusions by Meng et al. using Fbxo38KO/KO mice and cell systems. We have found no evidence indicating that FBXO38 controls the abundance and stability of PD-1.

cell biology↗

bioRxiv2020

Disruption of NAP1 genes supresses the fas1 mutant phenotype and enhances genome stability

Histone chaperones mediate assembly and disassembly of nucleosomes and participate in essentially all DNA-dependent cellular processes. In Arabidopsis thaliana, loss-of-functions of FAS1 or FAS2 subunits of the H3-H4 histone chaperone complex CHROMATIN ASSEMBLY FACTOR 1(CAF-1) has a dramatic effect on plant morphology, growth and overall fitness. Altered chromatin compaction, systematic loss of repetitive elements or increased DNA damage clearly demonstrate the severity of CAF-1 dysfunction. How histone chaperone molecular networks change without a functional CAF-1 remains elusive. Here we present an intriguing observation that disruption of the H2A-H2B histone chaperone NUCLEOSOME ASSEMBLY PROTEIN 1 (NAP1) supresses FAS1 loss-of function. The quadruple mutant fas1nap1;1-3 shows wild-type growth and decreased sensitivity to genotoxic stress. Chromatin of fas1nap1;1-3 plants is less accessible to micrococcal nuclease and progressive loss of telomeres and 45S rDNA is supressed. Interestingly, the strong genetic interaction between FAS1 and NAP1 does not occur via direct protein-protein interaction. We propose that NAP1;1-3 play an essential role in nucleosome assembly in fas1, thus their disruption abolishes fas1 defects. Our data altogether reveal a novel function of NAP1 proteins, unmasked by CAF-1 dysfunction. It emphasizes the importance of a balanced composition of chromatin and shed light on the histone chaperone molecular network.

molecular biology↗