Note for: Disruption of the BLM gene in ATM-null DT40 cells does not exacerbate either phenotype

Note for: Disruption of the BLM gene in ATM-null DT40 cells does not exacerbate either phenotype

(doi: 10.1038/sj.onc.1207276)

BLM and ATM;

1. autosomal recessive human disorder

2. immunodefficiency

3. genome instability

4. predisposition to develop cancer

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- BLM interact with ATM and recognize the abnormal DNA structures from the literature

- in DT40; BLM+ATM-KO viable

- no exacerbation of this KO is observed

- in the end, conclude that each protein has "largely" distinct roles in recognizing the DNA lesion-but there are some parts overlap.

ATM phosphorylates Nbs1 at Ser343-->stop Nbs to play role as lesion detection but change the function to be the adaptor and facilitating ATM-dependent phosphorylation of structural maintenance of structural maintenance of chromosome protein (SMC1)-->S-phase checkpoint

ATM-->phosphorylate FANCD2 on Ser222--> it is suggested the role in ATM-FA damage response.

Characteristic of BS-autosomal recessive disease;

1. immunodeficiency

2. infertility--(my guess it relates to meiosis)

3. erythemia

4. diabetes

5. genome instability--SCE increase

6. chromosomal break, deletion and rearrangments

7. increase level of leukemia and lymphoma

Literature indicated the interaction between ATM and BLM by which ATM phosphorylated BLM at Thr99 and Thr122 (after the cell has been injured by the radiation).

Radioresistant DNA synthesis is the characteristic of ATM KO --> bc there is the defect in G2-M checkpoint (based on DT40 study)

BLM KO in mice is hard to produce - embryonic lethal.

ATM KO in mice is also hard -- reduced growth rate, infertility

therefore, double KO will be hard.

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