MAD2L2
MAD2L2 (mitotic arrest deficient 2 like 2, also known as MAD2B, REV7, POLZ2 and FANCV) is an adapter protein that links DNA polymerases and repair factors in the cellular response to DNA damage. It also contributes to cell cycle control through the anaphase promoting complex. Browse Assay Genie's current range of MAD2L2 research reagents below, or read on for the biology behind the target.
MAD2L2 is an adapter protein that interacts with several different partners and takes part in more than one biological process. In translesion DNA synthesis it mediates the interaction between REV3L, the catalytic subunit of the error-prone DNA polymerase zeta, and the inserter polymerase REV1. This forms the second polymerase switch, which releases the replication blockade of replicative polymerases stalled at DNA lesions.
The MAD2L2 protein is also a component of the shieldin complex, which repairs DNA double-stranded breaks. During G1 and S phase the complex acts downstream of TP53BP1 to promote non-homologous end joining (NHEJ) and suppress DNA end resection. Through this activity it supports NHEJ-dependent processes such as immunoglobulin class-switch recombination and the fusion of unprotected telomeres. MAD2L2 may further influence the DNA damage response by regulating JNK-mediated phosphorylation and activation of the transcriptional activator ELK1.
In cell cycle control, MAD2L2 inhibits FZR1-mediated, and probably CDC20-mediated, activation of the anaphase promoting complex, thereby regulating cell cycle progression. NCBI describes it as a component of the mitotic spindle assembly checkpoint that is similar to MAD2L1 and can interact with ADAM9, ADAM15, REV1 and REV3. It also regulates TCF7L2-mediated gene transcription and may play a role in epithelial-mesenchymal transdifferentiation. The MAD2L2 gene belongs to the HGNC groups for DNA polymerases, Fanconi anaemia complementation groups and HORMA domain containing proteins, and the protein is localised to the nucleus, cytoplasm, spindle and chromosomes. Orthologues are annotated in mouse and rat as Mad2l2.
MAD2L2 bridges REV3L and REV1 to drive the polymerase switch that relieves replication blockade at DNA lesions.
As part of the shieldin complex, it acts downstream of TP53BP1 to promote NHEJ and limit DNA end resection.
It inhibits FZR1- and probably CDC20-mediated activation of the anaphase promoting complex, affecting cell cycle progression.
MAD2L2 mediates NHEJ-dependent processes including immunoglobulin class-switch recombination and fusion of unprotected telomeres.
MAD2L2 is an adapter protein. It connects REV3L and REV1 in translesion DNA synthesis, acts in the shieldin complex to promote non-homologous end joining of DNA double-strand breaks, and inhibits activation of the anaphase promoting complex to regulate cell cycle progression.
MAD2L2 is also known as MAD2B, REV7, POLZ2 and FANCV. The UniProt name is mitotic spindle assembly checkpoint protein MAD2B, and an earlier HGNC name was MAD2 (mitotic arrest deficient, yeast, homolog)-like 2. These names reflect its roles in the checkpoint and in DNA polymerase function.
NCBI notes that MAD2L2 is similar to MAD2L1, and both are HORMA domain proteins linked to the spindle checkpoint. Mouse and rat both carry a Mad2l2 orthologue. Check the datasheet of any product for its validated reactivity.
MAD2L1 and other mitotic checkpoint proteins, plus related targets with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9UI95; product specifications from Assay Genie datasheets.