Molecular Genetics II: Mutations, Repair and Cell Cycle Regulation

60 practice flashcards covering gene definition, mutations, DNA damage, repair mechanisms, and cell cycle concepts from the lecture notes.

What is the Central Dogma as described in the notes?

DNA → RNA → protein.

How is a gene defined in these notes?

A specific sequence of DNA with a start and stop point that specifies a polypeptide or functional RNA.

What distinguishes gene mutations from chromosomal mutations?

Gene mutations modify the DNA sequence of a single gene; chromosomal mutations involve larger changes in chromosome structure or number.

Name the types of DNA damage listed in the notes.

AP sites, single-strand breaks (SSBs), double-strand breaks (DSBs), and pyrimidine dimers.

List the DNA repair mechanisms mentioned.

Mismatch repair (MMR), Nucleotide excision repair (NER), Base excision repair (BER), Homologous recombination (HR), Non-homologous end joining (NHEJ), Translesional synthesis (TLS).

Which system recognizes hemi-methylated DNA in mismatch repair?

MutSHL system.

Which cancer syndrome is linked to defective mismatch repair?

Lynch syndrome (hereditary nonpolyposis colorectal cancer).

What is the role of NER and which diseases/genes are mentioned?

NER removes bulky lesions; associated with Xeroderma pigmentosum; BRCA1 is involved in ds-break repair.

Describe the BER pathway steps.

Damaged base is removed by DNA glycosylase → AP site forms → AP endonuclease cleaves → DNA polymerase I (β) fills the gap.

Which proteins are required for dsDNA break repair via HR?

BRCA1 and BRCA2.

What cancers are commonly associated with BRCA pathway defects?

Breast and ovarian tumors.

Describe Non-Homologous End Joining (NHEJ).

An error-prone repair pathway that can create insertions/deletions; contributes to Ig and TCR diversity.

What is Translesional synthesis (TLS) and its consequence?

Bypasses lesions during replication using low-fidelity polymerases (e.g., pol eta); can lead to mutations; linked to SCID and XP-variant when defective.

What regulates the cell cycle according to the notes?

Cyclins phosphorylate cyclin-dependent kinases (CDKs); tumor suppressors such as p53, p27, and Rb.

What is the ploidy of somatic cells and the order of the M phase?

Somatic cells are diploid; M phase: Prophase, Prometaphase, Metaphase, Anaphase, Telophase, Cytokinesis.

What is the ploidy and nature of sex cell division?

Sex cells are haploid; two cell divisions (Meiosis).

Describe oogenesis as presented.

Oogenesis completes before birth; oocytes paused at Prophase I at birth; meiosis continues during ovulation; meiosis II begins after fertilization; results in 1 large egg + 3 polar bodies.

Describe spermatogenesis as presented.

Begins at puberty and continuously produces sperm; yields 4 sperm per meiosis.

What happens during Prophase I of meiosis?

Chiasmata formation with crossing over between homologous chromosomes; independent assortment; nondisjunction can occur.

What is crossing over and why is it important?

Genetic exchange between homologous chromosomes, increasing genetic diversity.

What is nondisjunction?

Failure of chromosome pairs to separate properly during meiosis.

Describe gene structure components mentioned in the notes.

Promoter upstream; exons and introns; enhancers and proximal control elements; terminator; transcribed region downstream.

What are promoter region elements mentioned?

-35 box (TTGACA) and -10 box (TATAAT); transcription starts at +1.

Where are enhancers located and what do they do?

Upstream regulatory elements that increase transcription by binding regulatory proteins.

What is the function of a terminator?

Signals transcription termination.

What is the difference between wild type and mutant?

Wild type is the normal form; mutant is an altered form.

What are base substitutions and their subtypes?

Point substitutions (transitions/transversions); may be missense or nonsense.

What are insertions/deletions and their effect on reading frame?

Insertions/deletions can cause frameshift mutations.

Name chromosomal mutation types beyond substitutions and indels.

Inversions, translocations, and duplications.

What is the difference between null/knockout mutations and silent mutations?

Null/knockout abolish gene function; silent mutations do not change amino acid sequence.

What is an AP site?

An abasic site where the base is missing from the DNA backbone.

What are single-strand breaks (SSBs) and double-strand breaks (DSBs)?

SSBs break one DNA strand; DSBs break both strands.

What is a pyrimidine dimer?

A UV-induced lesion where adjacent pyrimidines form a covalent bond.

What is the role of BRCA1 in DNA repair?

BRCA1 is involved in double-strand break repair (HR pathway).

What is Xeroderma pigmentosum?

A disorder associated with defects in nucleotide excision repair (NER).

What is UvrABCD?

A bacterial NER complex; a key component of the NER pathway.

Which repair pathway is active in G1 and which in G2?

NER operates in G1; MMR is noted to function in G2.

When does homologous recombination primarily occur and why?

During S phase, when a sister chromatid is available as a template.

What does polymerase eta do in TLS?

Allows replication past lesions with low fidelity; error-prone, related to mutagenesis.

What is the relationship between cyclins and CDKs?

Cyclins phosphorylate and activate cyclin-dependent kinases (CDKs) to drive cell cycle progression.

Name the tumor suppressor genes mentioned.

p53, p27, Rb.

How do germline mutations differ from somatic mutations in terms of inheritance and disease?

Germline mutations are inherited; somatic mutations are acquired in cells and can lead to cancer.

What is the difference between exons and introns?

Exons are coding sequences kept in mature mRNA; introns are non-coding sequences removed during processing.

What is the start and stop point in a gene used for?

They specify the coding region that encodes the polypeptide or functional RNA.

What are consensus sequences in promoters?

Conserved sequences recognized by transcription machinery (e.g., TTGACA and TATAAT in promoters).

Where is the transcribed region located relative to the promoter?

Downstream of the promoter; within the transcribed region.

What is the role of the promoter region's -35 and -10 boxes?

They are conserved promoter elements that direct transcription initiation.

What is the function of the transcription start site (+1)?

Marks where transcription begins.

What is the significance of the 'inter-base distance' in promoters?

Optimal spacing between promoter elements influences transcription efficiency.

What is the meaning of 'promoter' region in bacteria vs eukaryotes as per notes?

Promoters are upstream DNA elements that recruit RNA polymerase; notes show bacterial promoter examples with -35 and -10 boxes.

What is the clinical relevance of BRCA pathway defects beyond cancer risk?

Associated with susceptibility to certain drugs that induce lesions in DNA.

What is the role of the DNA glycosylase in BER?

It recognizes and removes damaged bases, initiating BER.

What is the role of AP endonuclease in BER?

It cleaves the backbone at the AP site created after base removal.

What is the role of DNA polymerase in BER?

Fills in the gap after AP endonuclease action (often Pol I or Pol β depending on context).

Which repair pathway is described as not being true repair but bypass?

Translesional synthesis (TLS).

What is the consequence of TLS being error-prone?

Increases risk of mutations; can contribute to genetic disease when defective or mutagenic.

What are the two major sources of mutagens discussed?

Chemicals (alkylating agents, base analogues, intercalating agents, cross-linking agents) and radiation (ionizing vs UV); heat is also listed.

Name examples of chemical mutagens mentioned in the notes.

Alkylating agents, base analogues (bromouracil), intercalating agents (acridine orange), cross-linking agents (cisplatin).

What types of radiation are mutagenic according to the notes?

Ionizing radiation and UV radiation.

What happens when DNA damage is not repaired properly in germ cells vs somatic cells?

Germ cell mutations can be inherited; somatic cell mutations can lead to cancer.

What is the significance of the 'consensus sequences' in promoter regions?

They are common sequences recognized by transcription machinery, guiding transcription initiation.

What is the difference between point mutations and silent mutations?

Point mutations change one nucleotide; silent mutations do not alter the amino acid sequence.

Which cellular process ensures genetic diversity during meiosis?

Crossing over and independent assortment during Prophase I.

Which repair pathway is known to produce Ig and TCR diversity?

Non-Homologous End Joining (NHEJ) or the context of immune system diversity mentioned with NHEJ.

What is the role of BRCA2 in DNA repair?

BRCA2 works with BRCA1 in double-strand break repair via HR.

What are exons and introns in gene structure?

Exons are coding sequences; introns are non-coding sequences spliced out.

What does 'transcribed region' refer to?

The portion of DNA that is transcribed into RNA.

What is the effect of promoter mutations on transcription?

Can alter transcription start and level of gene expression.

What is the 'start point' in transcription?

The transcription start site, designated as +1.

What is the 'downstream' direction in transcription?

Direction of transcription after the transcription start site.