Caracterização funcional de componentes da resposta ao dano DNA em Aspergillus nidulans: os genes chkA, chkB e ddbA / Functional Characterization of DNA damage response components in Aspergillus nidulans: the ddbA, chkA and chkB genes.

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

The constant exposure of different organisms to agents that damage the DNA structure, has provided the cells with repair mechanisms that are conserved during evolution. In mammal cells, the DNA damage repair pathways and the cell cycle checkpoint regulation act together to prevent cell cycle progression before the repair is performed avoiding mutation fixaxion. However these responses are complex and demand overlapping functions and the intersection of many metabolic pathways. NER is an important mechanism in the process that recognize and remove cyclobutane pyrimidine dimers and 6-4 pyrimidine-pyrimidone photoproduct from the DNA structure. In mammals seven complementation groups for XP deficient cells were identified. One of these groups is XPE, known for having strong affinity to the DNA damage caused by UV light and is formed by two subunits DDB1 and DDB2. A search on the Aspergilus nidulans database using a Homo sapiens DDB1 sequence, revealed a single ORF with relevant similarity. The A. nidulans homologue was deleted and named DdbA. ddbA does not have significant similarity to DDB2 protein. In A. nidulans the protein DdbA is involved on the DNA damage repair caused by UV light and 4NQO. Additionaly ddbA is genetically interacting with uvsBATR, histone H2AX and cshBCSB the damage repair caused by MMS , BLEO, 4NQO and UV light. Also, an analysis of the gene ddbA expression indicated that it is induced by MMS, BLEO, 4-NQO, oxidative stressing agents and by the assexual and sexual development processes of A. nidulans. We also verified that the sub-cellular localization of DdbA was not affected by the presence of UV light or 4-NQO indicating that the protein DdbA is constitutively present in the nucleus. In S. pombe, the serine treonine kinases CHK1 and CHK2 proteins were identified as essential to the Sphase blockage in response to the DNA damage or replicational stress. These kinases are phosphorilated by ATR and ATM kinases, respectively and have been extensively characterized in A. nidulans. In this fungus, the proteins ChkACHK1 and ChkBCHK2 are involved on the DNA damage response and are genetically interacting in an epistatic and/or synergistic manner with the AtmAATM and UvsBATR kinases. Our results also sugest that the proteins ChkA and ChkB may also be involved in meiosis and act in a complementary way during the S-phase block. Furthermore the AtmA, ChkA, ChkB e UvsB proteins are complementary redundant for the maintenance of the polar growth in A. nidulans.

ASSUNTO(S)

polar growth. chka ddba dna damage chkb chka ddba crescimento polar aspergillus nidulans dano ao dna keywords: aspergillus nidulans

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